International Journal of Current Research and Review
ISSN: 2231-2196 (Print)ISSN: 0975-5241 (Online)
logo
slider
slider
slider
slider
Bootstrap Slider

Indexed and Abstracted in: Crossref, CAS Abstracts, Publons, Google Scholar, Open J-Gate, ROAD, Indian Citation Index (ICI), ResearchGATE, Ulrich's Periodicals Directory, WorldCat (World's largest network of library content and services)

Search Articles

Track manuscript

Full Html

IJCRR - 4(7), April, 2012

Pages: 89-100

Date of Publication: 18-Apr-2012


Print Article   Download XML  Download PDF

BIOLOGICAL ACTIVITY AND ANALYTICAL CHARACTERIZATION OF BARBITURIC ACID

Author: Vijaya Laxmi S, Janardhan B, Rajitha B

Category: General Sciences

Abstract:Earlier literature reports imply that this scaffold is having activity on central nervous system. According to the present studies it has become an attractive target for the development of drugs, which hold variety of biological activities. Derivatives of barbituric acid have attracted the attention of researchers in synthetic organic chemistry, as well as medicinal chemistry, for a long time as a result of their exceptionally diverse biological activity. Present review highlights the importance of the barbituric acid in the present context.

Keywords: Barbituric acid, Biological activity, Spectral studies, X-ray Crystallography, Dye properties.

Full Text:

1 INTRODUCTION
Barbituric acid (BA) is documented as the parent compound of the barbiturate drugs. (Fig.1). It is used in the production of riboflavin, Nembutal, and Phenobarbital.1-2 This class of compounds has been extensively used in medical and biological studies for many years, the best known of which is their sedative action in the central nervous system3 (CNS).

It was demonstrated that some barbituric acid derivatives have new and very interesting biological activities that stand apart from previous medical utilization of barbituric acid derivatives.4 However it is a precursor to barbituric acid derivatives widely been used in the manufacturing of plastics,5 textiles,6 polymers,7 and pharmaceuticals,8-9 dental materials,10 water thinned or oil-based inks,11 and as polymerization catalysts.12 In view of the above observations it is worthwhile to make a brief review on it. 2 Barbiturates 2.1 Chemistry of Barbiturates Barbituric acid an organic compound of the pyrimidine family,13 chemically called as 2,4,6 trioxopyrimidine, a class of compounds with a characteristic six-membered ring structure composed of four carbon atoms and two nitrogen atoms. Compounds possessing the C2=O group are known as oxybarbiturates, and those having a C2=S group are known as thiobarbiturates.

The thiobarbiturates generally have higher lipid solubilities than their corresponding oxybarbiturates. The α-carbon has a reactive hydrogen atom and is quite acidic, variety of barbituric acid drugs were synthesized by employing Knoevenagel condensation. Their biological activities varied when substituent‘s introduced on two Nitrogen atoms and 5th position of barbituric acid. (Fig. 2) 2.2 Synthesis of Barbituric acid Several synthetic methods are available in the literature. In 1862, A. V. Baeyer accidentally discovered the barbituric acid, by combining urea and malonic acid on condensation reaction.14 2.3 Synthesis of Barbiturate drugs Barbituric acid condense smoothly with aldehydes under moderate conditions,15-17 yielding 5-ylidene.The presence of low electron density at the C-5 position in the exocyclic C=C bond, owing to conjugation with the carbonyl groups in the 4 and 6-positions, causes the nucleophilic addition reaction. Several literature procedures were reported for the Knoevenagel condensation of substituted benzaldehydes and barbituric acid.18-19 Jursic20 performed the condensation of barbituric acid substituted benzaldehydes in excess of methanol solution without adding any external acid or base catalyst. Uncatalysed Knoevenagel condensation of barbituric acid and substituted benzaldehydes in aqueous medium at room temperature was reported by Mohit L. et al. 21 Solvent-free Knoevenagel condensations of barbituric acid under solid state, synthesis was achieved by Gerd Kaupp et al.22 2.4 Tautomerism Barbituric acid exists in the solid state in the trioxo structure as shown by X-ray23-24 and 14NNQR25 methods. NMR investigation of the oxohydroxy equilibrium also indicates that only the oxo form is present in a solution in anhydrous DMSO.26, 27 BA exist as single molecular species in the gas phase with trioxo tautomers being the most stable. This conclusion was reached on the basis of calculated tautomer energies and FT-IR spectra.28 Igor Novak et al. have used G3MP2B3 method to calculate Gibbs free energies of the two possible tautomers established that keto tautomers are more stable than enols by 36.8 and 36.7 kJ/mol, respectively.29 Recently Michale R.Chierothi et al. reported that by griding a commercial sample of Barbituric acid in its trioxo form for 24 h, a new compound has been isolated. The new phase has been identified as trihydroxy isomer. 30 Ab inito and density functional theory (DFT) methods were used to study the tautomers of barbituric acid in the gas phase and in a polar medium, this method was concluded that the triketo form of barbituric acid is found to be the most stable form in the gas phase and in solution. Tautomers, which are partially, enolized forms, have higher dipolemoments in gas phase are stabilized in polar medium.31 2.5 Spectral studies on Barbituric acid UV-Vis, IR spectra, Raman spectroscopy, NMR and Mass spectrometry details for BA discussed by Jacek T. Bojarski et.al.32 2.6 X-ray studies Crystallographic data show that barbiturates generally have low symmetric crystal systems, i.e., monoclinic or sometimes triclinic. Sadad Al-Saqqar et al. reported the X-ray diffractometric analysis of barbituric acid (1,4)- dioxane solvate confirmed the two nitrogen atoms of the acid act as hydrogen donors to two oxygen atoms, each from a different molecule of (1,4)-dioxane.33 (Fig.3.) Maria Victoria Roux et al. reported the calorimetric, computational, and powder Crystallographic Study of barbituric acid 34 and Single crystal X-ray Crystallographic study has been done for the compound 5,5dimethyl Barbituirc acid.35 Crystallization of Polymorphs of Phenobarbital was reported by Neslihan Zencirci et al.36 Mechanically Induced Phase Change in Barbituric acid was achieved by Michele R. Chierotti, et al. By grinding a commercial sample of barbituric acid in its trioxo form (polymorph II, 99%) for 24 h, a new compound has been isolated.

The new phase has been identified as the trihydroxyl isomer. 2.7 Thermogravimetric analysis and Thermophysical Study According to Alexandre Berlin et al. made thermogravimetric characteristics of barbituric acid and its derivatives they indicates the degrees of hydration as well as the range of stabilities of the anhydrous compounds. The decomposition of barbital has also been made to study the effect of alkyl substituent‘s in the 5 position on the decomposition. The differential thermal analysis for dilituric acid showed a sharp exotherm at 190o indicating a violent explosion.37 Manuel Temprado et al. reports a differential scanning calorimetry (DSC) study of some of the barbituric acid derivatives.38 Electron paramagnetic resonance study of thermal decomposition of barbituric acid can be studied by J. N. Herak et al. the structures of the detected radicals in the decomposition of the barbituric acid derivatives suggest that there are various ways of decomposition of these substances. In all the analyzed compounds a loss of the substituent group R1 or R2 is detected. The loss of R1 or R2 is not necessarily decomposition for all the molecules other competitive decomposition pathways are possible. These experiments undoubtedly prove that in thermal decomposition of molecules free radicals may be found.39 4 Dyes Many Barbituric acid derivatives such as Thiobarbituric acid and its derivatives also been used in the synthesis of dyes and pigments or intermediates in the preparation of Dyes.40,41 Barbituric acid has been used as disperse dyes with strong fluorescent and as yellow organic pigments,5 and investigated as stain developers for the identification of nucleic acids.42 Isidor greenwald investigated that by the addition of alcohol to a mixture of solutions of barbituric acid, picric acid and sodium hydroxide, a red precipitate is obtained.43 The barbituric acid group present in the yellow and orange iso indolinone and azo pigments provides hydrogen bonding within these pigment systems giving them good durability but this still falls short of the standard required for automotive quality. The synthesis, characterisation and properties of some polycyclic barbiturate pigments are described. The pigments have been tested as colourants for plastic and paint and the results of lightfastness, heatfastness and contact bleed tests are reported by D. Thetford et al. results suggest that only the barbiturate pigments with large aromatic moieties such as the pyren-1-yl and fluoren-2-yl substituent‘s have good lightfastness properties at reduced shades in plastics.5 Novel heterocyclic disazo barbituric acid dyes were synthesized and solvatochromic properties were studied (Fig.4. and Fig.5.) The effects of varying the pH and solvent on the absorption of the dyes substituted with electronwithdrawing and electron-donating groups at their o-, m-, and p-position were examined in detail.44 Some other literature reports also well documented about the dyes properties of the barbituric acid.45-475 Biological Activities of Barbituric acid Barbiturates are 6-oxo derivatives of uracil, a component of the nucleic acids. This similarity may be important since barbiturates have been found to associate preferentially with adenine2 analogous to the uracil-adenine binding in nucleic acids. The strong interaction observed between barbiturates and adenine led to the suggestion that the barbiturates exert their biological activity by specifically binding and inactivating a variety of molecules containing adenine, including coenzymes and adenosine 5‘triphosphate,48 they bind to specific regions of various receptors e.g. to GABA, nicotinicacetylcholine (nAChR) or BK channel receptors which are all ligand-gated ion channels,49 the binding to the GABA receptor requires that C5 substituted by alkyl or aryl groups. The substitution enhances lipid solubility and facilitates transport of BA towards their enzyme targets.29 5.1. CNS Depressant activity It is important to note that Barbituric acid itself has no CNS activity. Barbituric acid ring as well as the C(5) lipophylic side chains known to be necessary for CNS activity. CNS activity obtained by substitution certain alkyl, alkenyl or aryl groups on pyrimidine ring structure.

Edwared. Smmissm et al. reported the synthesis of Acyloxy alkyl barbiturates as Potential LongActing Central Nervous System Depressants.50 (Fig.6.) Recently José D. Figueroa-Villar et al. investigated the synthesis of a new family of barbiturates, 5-chloro-5-benzylbarbituric acids using a simple efficient synthetic method from aromatic aldehydes and barbituric acid, followed by reduction and chlorination with trichloroisocyanuric acid in vivo evaluation with mice showed that these compounds are having tranquilizing activity. The obtained data clearly indicate that the most active compounds are those with substituent‘s at the ortho position51 (Fig.7.)

5.2. Antiinflamatory activity A novel series of barbituric acid derivatives were identified as selective inhibitors of α4β7- MAdCAM (mucosal addressin cell adhesion molecule-1) and investigated the structure– activity relationships of the barbituric acid for their ability to inhibit the interaction between α4β7 and MAdCAM out of all the synthesized compounds 3-indolyl barbituricacid derivative (Fig.8.) exhibited potent activity at 0.06 (μM), 3-indolyl was identified as an important pharmacophore component.52 A series of 1,3- diphenylharbituric acid derivatives has been prepared and evaluated for antiinflammatory activity by means of the Randall-Selitto test,53 and the pleural effusion method, the compounds are found to be toxic and less active than phenylbutazone by the

testing procedures used. 1,3-diphenyl-5-(3- methyl-2-butenyl)barbituricacid (Fig.9.) was identified as the most potent member of the series.54 5.3. Anti cancer activity By combining indole and barbituric acid, new hybrid molecules were designed and synthesized. Evaluations of these molecules over 60 cell line panel of human cancer cells.

 

From all the synthesized compounds 5-((1-allyl1H-indol-3yl)methylene)pyrimidine2,4,6(1H,3H,5H)-trione (Fig.10.) and 5-((1-allyl1H-indol-3yl)methylene)- 1,3dimethylpyrimidine-2,4,6(1H,3H,5H)-trione (Fig.11.) has shown significant anticancer activity. Dockings of these active molecules in the active sites of COX-2, thymidylate synthase and ribonucleotide reductase indicate their strong interactions with these enzymes.55 5- benzyl (Fig.12.) and 5-benzylidene (Fig.13.) derivatives useful in Uridine Phosphorylase inhibitors in cancer theraphy. Inhibition of Uridine Phosphorylase of these compounds equal to or greater than that of their acyclouridine counterparts.56 Various Barbituric acid derivatives which are having significant anticancer activities were reported in the literature. 57, 58

5.4. Anti Bacterial Activity Ayoob Bazgira et al. described a one-pot and efficient method for the synthesis of pyrazolo [4',3':5,6]pyrido[2,3-d]pyrimidine-dione (Fig.14.) derivatives by condensation reaction of barbituric acids, 1H-pyrazol-5-amines and aldehydes under solvent- free conditions. All the products were evaluated for antimicrobial activity.

 

Almost most of the compounds exhibited good to excellent antibacterial activity against all the tested strains.59 Huacan Song et al. reported the synthesis and antimicrobial activity of 5-(4- hydroxybenzylidene)-dihydro-2- thioxopyrimidine-4,6(1H,5H)-dione (Fig.15.) and 5-(4-hydroxybenzyledene)pyrimidine2,4,6(1H,3H,5H)-triones (Fig.16.) and found to be most potent inhibitors with IC50 value of 14.49 μM and, 13.98 μM respectively.60

 

5.5. Antituberculosis activity Recently we reported the synthesis of novel barbiturates and thiobarbiturate analogs of Furano chromene carbaldehydes and dihydropyranochromenes and evaluated for their antitubercular activities against Mycobacterium tuberculosis H37RV, and cytotoxicity (CC50) in the VERO cell MABA assay. The results indicate pyranochromene analog showed good antitubercular activity (IC90: 5.9 µg/mL) and cytotoxicity (CC50: 14.27 µg/mL). antitubercular activity of 5-(6,10-Dimethyl-4,8-dioxo-4,8- dihydropyrano[3,2-g]chromen-3-yl)methylene)- pyrimidine-2,4,6(1H,3H,5H)trione (Fig.17.) was superior to the antituberculosis drug, pyrazinamide (PZA; IC90: >20 µg/mL).61

 

5.6. Analgesic activity In Analgesics 1 Julius A. Vida et al. reported the synthesis of 5-substituted 5- propionoxybarbituric and evaluated for analgesic activity. One compound, 5- propionoxy-5-(1-phenylethy1)barbituric acid, (Fig.18.) displayed better analgesic activity than codeine orally and had half the analgesic potency of morphine when administered subcutaneously.62 In Analgesics 2 same authors (Julius A. Vida et al.) synthesized the acyloxy, trialkylsilyloxy, triphenylsilyloxy, and tosyloxy derivatives of 5-(1-phenylethy1)barbituric acids from all the synthesized compounds 5-acetoxy5-(l-phenylethyl)barbituricacid (Fig.19) and 5- cyclopropylcarbonyl-oxy-5-(lphenylethyl)barbituricacid (Fig.20.) exhibited better analgesic activity than codeine orally.63

 

5.7. Protein Tyrosine Phosphatase Inhibitor protein tyrosine phosphatase are key regulators of the phosphorylation of proteins involved in cellular signal transduction pathways. New series of barbituric acid derivatives synthesized and evaluated protein tyrosine phosphate inhibitory activity. 5-(2,4bis(4- (trifluoromethyl)benzyloxy)benzylidene)pyrimid ine-2,4,6(1H,3H,5H)-trione (Fig.21.) was proved most potent with an IC50 value of 10μM. 64

 

5.7. Protein Tyrosine Phosphatase Inhibitor protein tyrosine phosphatase are key regulators of the phosphorylation of proteins involved in cellular signal transduction pathways. New series of barbituric acid derivatives synthesized and evaluated protein tyrosine phosphate inhibitory activity. 5-(2,4bis(4- (trifluoromethyl)benzyloxy)benzylidene)pyrimid ine-2,4,6(1H,3H,5H)-trione (Fig.21.) was proved most potent with an IC50 value of 10μM. 64

 

5.9. Anti Diabetic activity Peroxisome proliferator-activated receptor (PPAR) belongs to the nuclear hormone receptor (NHR) superfamily.1 Three subtypes, PPARα, PPARγ and PPARδ, for this receptor has been identified and found to be important targets for the treatment of type 2 diabetes, dyslipidemia, atherosclerosis. Etc66 A new series of PPARγ ligands based on barbituric acid (BA) has been designed for virtual screening and molecular docking. Out of the total 14 molecules, 6 were found to bind to the murine PPARγ with IC50 ranging from 0.1 to 2.5 μM as compared to reference standard, pioglitazone (IC50 = 0.7μM).67 Lijuan Chen et al. evaluate the protective effect and the mechanism of the novel agonist of PPARγ on NAFLD model using one of the compounds, 68 5-(4- (benzyloxy)benzylidene)pyrimidine2,4,6(1H,3H,5H)-trione (Fig.23.) Same authors in another report synthesized forty-four novel barbituric and thiobarbituric acid derivatives against non-alcoholic fatty liver disease (NAFLD) This disease is closely associated with insulin resistance and metabolic syndromes including obesity, type II diabetes.

 

From all the synthesized compounds four compounds were found to increase the expression of adiponectin and lower the leptin level in 3T3-L1 adipocytes at respective concentration of 10 μM. Among them, N(Pyridin-2-yl)-2-(4-((2,4,6- trioxotetrahydropyrimidin-5(6H)- ylidene)methyl)phenoxy)acetamide (Fig.24.) showed the most efficacious and orally active molecule for reducing fat deposition against non-alcoholic fatty liver disease.69 6

ACKNOWLEDGEMENTS
Authors would like to thank the IICT and CFRD Hyderabad for providing the library facility to complete the literature review.

CONCLUSION
From these observations it clearly indicates barbituric acid not only having CNS depressant activity but acts as an important pharmacophore having new and very interesting biological activities such as anti cancer, antitubercular,anti inflammatory, analgesic, and antimicrobial activities and also functioned as dyes and pigments. This review will give scope for the future investigations on this scaffold.

References:

1. Marcus K .C. Chao, Kenneth S. Albert, Salvatore A . Fusari. Analytical Profiles of Drug Substances 7, 359 (1978)

2. (a) R. Rastaldo, C. Penna, P. Life Sci 69, 729 (2001) (b) S. P. Aiken, W. M. Brown. Front. Biosci 5, 124 (2000) (c) E. Ghansah, D. S. Weiss. Neuropharmacology 40, 327 (2001)

3. N.B. G. Taylorn, R . L. Noble. Nature 163, 447 (1949)

4. (a) A. Oliva, G. Zimmermann, H.-W. Krell. International Patent WO 98/58925, 1998. (b) K. S Gulliya, Uses for barbituric acid analogs. U.S. patent 943,385, 1997.

5. D. Thetford, A. P. Chorlton, J. Hardman. Dyes and Pigments 59, 185 (2003)

6. R. Bartzatt. J. Pharm. Biomed. Anal 29, 909 (2002)

7. (a) R. Andreu, J. Garin, J. Orduna, R. Alcala, B. Villacumpa. Org. Lett 5, 3143 (2003) (b) N. D. McClenaghan, C. Absalon, D. M. Bassani. J. Am. Chem. Soc 125, 13004 (2003)

8. M. Meusel, A. Ambrozak, T. K. Hecker, M. Gutschow. J. Org. Chem 68, 4684 (2003)

9. (a) D. M. Neumann, B. S. Jursic, K. L. Martin. Tetrahedron Lett 43, 1603 (2002) (b) B. S. Jursic, D. M. Neumann. Tetrahedron Lett 42, 8435 (2001)

10. (a) R. Lusck, Polymerizable dental material. Eur. Pat. Appl. EP 1972767, 2008; (b) N. Moszner, U. K. Fischer, P. Burtscher, J. Angermann, V. Rheinberger, Dental materials with improved compatibility. Eur. Pat. Appl. EP 157452, 2005.

11. Ch. Nozaki. Jpn. Kokai Koho Patent P2001294781 A 20011023, 2001.

12. A. D. Johnston. U.S. Pat. Appl. US 2003215635, 2003.

13. I. L. Finar, ?Organic chemistry, stereochemistry and the chemistry of natural products?, 5th ed., Longman Group, Ltd., London. 2, 627 (1975)

14. A . Von Baeyer. Ann . Chem . Pharm 130, 129 (1864)

15. M. Sekiya, C.Yanaihara. Chem. Pharm. Bull 17, 747 (1969)

16. G. Haas, J. L. Stanton, A. Sprecher, P. Wenk. J . Heterocycl. Chem 18, 607 (1981)

17. Cherkupally Sanjeeva Reddy, Adki Nagaraj. Chinese Chemical Letters

18, 1431 (2007) 18. E. Obrador, M. Castro, J. Tamariz, G. Zepeda, R. Miranda, F. Delgado. Synth. Commun 28, 4649 (1998)

19. G. Alcerreca, R. Sanabria, R. Miranda, G. Arroyo, J. Tamariz, F. Delgado. Synth. Commun 30, 1295 (2000)

20. B.S. Jursic. J. Heterocycl. Chem 38, 655 (2001)

21. Mohit L. Deb and, Pulak J. Bhuyan. Tetrahedron Letters 46, 6453 (2005) 22. Gerd Kaupp, M. Reza Naimi-Jamal, Jens Schmeyers. Tetrahedron 59, 3753 (2003)

23. G. A. Jeffrey, S. Chose, J. O. Warwicker. Acta Crystallogr 14, 881 (1961)

24. W. Bolton, Acta Crystallogr 16, 166 (1963)

25. T. Maruizumi, Y. Hiyama, E. Niki. Bull. Chem. Soc. Jpn 53, 1443 (1980)

26. G. A. Neville D. Cook. Can. J. Chem 47, 743 (1969).

27. J. A. Glasel. Org. Magn. Reson 1, 481(1969) 

28. (a) F. Zuccarello, G. Buemi, C. Gandolfo, A. Contino. Spectrochim. Acta. A 59, 139 (2003) (b) F. Ramondo, A. Pieretti, L.Gontrani, L. Bencivenni. Chem. Phys 271, 293 2001.

29. Igor Novak, Branka Kovac. Chemical Physics Letters 493, 242 (2010)

30. Michele R. Chierotti, Roberto Gobetto, Luca Pellegrino, Luciano Milone, Paolo Crystal Growth and Design . 8, 1454 (2008)

31. K. Senthilkumar, P. Kolandaivel. Journal of Computer-Aided Molecular Design 16, 263 (2002)

32. Jacek T. Bojarski, Jerzy L. Mokrosz, Henryk J. Barton, Maria H. Paluchowska, Advances in heterocyclic chemistry. 38, 227 (1985)

33. Sadad Al-Saqqar, Larry R. Falvello, Tatiana Soler. Journal of Chemical Crystallography. 34, 61 (2004)

34. Maria Victoria Roux, Manuel Temprado, Rafael Notario, Concepcion Foces-Foces, Vladimir N. Emel yanenko, Sergey P. Verevkin. J. Phys. Chem. A. 112, 7455 (2008)

35. Marria Victoria Roux, Rafael Notario, Concepcion Foces-Foces, and Manuel Temprado. J. Phys. Chem. A 114, 3583 (2010)

36. Neslihan Zencirci, Thomas Gelbrich, Volker Kahlenberg, Ulrich J. Griesser. Crystal Growth and Design 9, 3444 (2009)

37. Alexander Berlin, Murray E.Taylor, Rex J. Robinson. Analytica Chemica Acta 24, 427 (1961)

38. Manuel Temprado, Maria Victoria Roux, Francisco Ros, Rafael Notario,Marta Segura, James S. Chickos. J. Chem. Eng. Data 56, 263 (2011)

39. J. N. Herak, J. J. Herak. J. Am. Chem. Soc 94, 7646 (1972)

40. H. Gysling, G. Schwarzenbach. Helv.Chim.Acta 32, 1484 (1949)

41. H. Schmidt. Anstrichmittel. 61, 881 (1959)

42. D. Popov, B. Thorell. Stain Technology 57, 143 (1982)

43. Isidor greenwald. J. Am. Chem. Soc 50, 1469 (1928)

44. Fati Karci, Fikret Karci. Dyes and Pigments 77, 451(2008)

45. Yukinori Nagao, Toshifumi Sakai, Kozo Kozawa, Toshiyuki Urano. Dyes and Pigments 73, 344 (2007)

46. Marcos Caroli Rezende, Paola Campodonico, Elsa Abuin, Jean Kossanyi, Spectrochimica Acta Part A 57, 1183 (2001)

47. Patricio Flores, Marcos Caroli Rezende, Francisco Jara. Dyes and Pigments 62, 277 (2004)

48. (a) Y. Kyogoka, R. C. Lord, R. Rich. Nature (London) 1968; 218: 69-72 ; (b) D. Voit, R. Rich, J. Amer. Chem. Soc 94,1972 (5888)

49. (a) H.R. Arias, E.A. McCardy, M.J. Gallagher, M.P. Blanton. Mol. Pharmacol 60, 497(2001) (b) T. Morimoto, K. Sakamoto, H. Sade, S. Ohya, K. Mol. Pharmacol 71, 1075 (2007)

50. Edwared. Smmissm, raonb, erta . robinson Marcia arehart Buckwalter. J. Med. Chem 14, 853 (1971)

51. Andreia A. Vieira, Niele M. Gomes, Maria E. Matheus, Patricia D. Fernandes , José D. Figueroa-Villar. J. Braz. Chem. Soc 22, 364 (2011)

52. Geraldine C. Harriman, Matthias Brewer, Robert Bennett, Cyrille Kuhn, Marc Bazin, Greg Larosa, Paul Skerker, Nancy Cochran, Debra Gallant, Deborah Baxter, Dominic Picarella, Bruce Jaffee, Jay R. Lul Michael J. Briskin. Bioorg. Med. Chem. Lett 18, 2509 (2008).

53. L. O. Randall, J. J. Selitto, drch. Intern. Phormacodyn 111, 409 (1957)

54. A. J. Vazakas, W. Walden Bennetts. J. Med. Chem 7, 342 (1964)

55. Palwinder Singh, Matinder Kaur, Pooja Verma. Bioorg . Med. Chem. Lett. 19, 3054 (2009)

56. Fardos N.M.Naguib, Mahmoud H, Raymond Panzica, Narragansett. US.patent 5,141,943, 1992.

57. D. Brewer. US. patent 4,920,126, 1990.

58. Ambrogio olive, Gilianpiero Dechillis, Frank Grams, valeria Livi, Gerd Zimmermann, Erresto menta, Hans Willi krell. US patent 6,335,332 B1, 2002.

59. Ayoob Bazgira, Maryam Mohammadi Khanaposhtani, Ali Abolhasani Soorki. Bioorg. Med. Chem. Lett. 18, 5800 (2008)

60. Qin Yan, Rihui Cao, Wei Yi, Zhiyong Chen, Huan Wen, Lin Ma, Huacan Song. Eur. J. Med. Chem 44, 4235 (2009)

61. Vijayalaxmi S, Thirupathi Reddy Y, Suresh Kuarm B, Narsimha Reddy P, Peter A. Crooks, Rajitha B. Bioorg. Med. Chem. Lett. 21, 4329 (2011)

62. Julius A. Vida, Carlos M. Samour, Mary H. O‘Dea, Theodore S. T. Wang, William R. Wilber, John F. Reinhard . J. Med. Chem 17, 772 (1974)

63. Julius A. Vida, Carlos M. Samour, Mary H. O‘Dea, Theodore S. T. Wang. J. Med. Chem 17, 1194 (1974)

64. Bhooshan Kafle, Bharat Raj Bhattarai, Hyeongjin Cho. Bull. Korean Chem. Soc. 32,31 (2011)

65. Thirupathi Reddy Y, Konjeti R. Sekhar, Nidhish Sasi, Narsimha Reddy P, Michael L. Freeman, Peter A. Crooks. Bioorg. Med. Chem. Lett. 20, 600 (2010)

66. (a) L. Guo, R. Tabrizchi. Pharmacol. Ther 111, 145 (2005) (b) S. Kersten. Eur. J.Pharmacol 440, 223 (2002) (c) C. Duval, G. Chinetti, F. Trottein, J. Fruchart, B.Staels, Trends Mol. Med. 8,422 (2002).

67. Sandeep Sundriyal, Bhoomi Viswanad, Poduri Ramarao, K. Asit, Chakraborti, V. Prasad, Bharatam. Bioorg. Med. Chem. Lett 18, 4959 (2008)

68. Hao Zheng, Shilin Li, Liang Ma, Ling Cheng, Chongyang Deng, Zhizhi Chen, Caifeng Xie, Mingli Xiang, Wei Jiang, Lijuan Chen. European Journal of Pharmacology 659, 244 (2011)

69. Liang Ma, Shilin Li, Hao Zheng, Jinying Chen, Lin Lin, Xia Ye, Zhizhi Chen, Qinyuan Xu, Tao Chen, Jincheng Yang, Neng Qiu, Guangcheng Wang, Aihua Peng, Yi Ding, Yuquan Wei, Lijuan Chen. Eur. J. Med. Chem 46, 2003(2011)

Announcements

Dr. Pramod Kumar Manjhi joined Editor-in-Chief since July 2021 onwards

COPE guidelines for Reviewers

SCOPUS indexing: 2014, 2019 to 2021


Awards, Research and Publication incentive Schemes by IJCRR

Best Article Award: 

One article from every issue is selected for the ‘Best Article Award’. Authors of selected ‘Best Article’ are rewarded with a certificate. IJCRR Editorial Board members select one ‘Best Article’ from the published issue based on originality, novelty, social usefulness of the work. The corresponding author of selected ‘Best Article Award’ is communicated and information of award is displayed on IJCRR’s website. Drop a mail to editor@ijcrr.com for more details.

Women Researcher Award:

This award is instituted to encourage women researchers to publish her work in IJCRR. Women researcher, who intends to publish her research work in IJCRR as the first author is eligible to apply for this award. Editorial Board members decide on the selection of women researchers based on the originality, novelty, and social contribution of the research work. The corresponding author of the selected manuscript is communicated and information is displayed on IJCRR’s website. Under this award selected women, the author is eligible for publication incentives. Drop a mail to editor@ijcrr.com for more details.

Emerging Researcher Award:

‘Emerging Researcher Award’ is instituted to encourage student researchers to publish their work in IJCRR. Student researchers, who intend to publish their research or review work in IJCRR as the first author are eligible to apply for this award. Editorial Board members decide on the selection of student researchers for the said award based on originality, novelty, and social applicability of the research work. Under this award selected student researcher is eligible for publication incentives. Drop a mail to editor@ijcrr.com for more details.


Best Article Award

A study by Dorothy Ebere Adimora et al. entitled \"Remediation for Effects of Domestic Violence on Psychological well-being, Depression and Suicide among Women During COVID-19 Pandemic: A Cross-cultural Study of Nigeria and Spain\" is awarded Best Article of Vol 14 issue 23
A study by Muhas C. et al. entitled \"Study on Knowledge & Awareness About Pharmacovigilance Among Pharmacists in South India\" is awarded Best article for Vol 14 issue 22
A study by Saurabh Suvidha entitled \"A Case of Mucoid Degeneration of Uterine Fibroid with Hydrosalphinx and Ovarian Cyst\" is awarded Best article of Vol 14 issue 21
A study by Alice Alice entitled \"Strengthening of Human Milk Banking across South Asian Countries: A Next Step Forward\" is awarded Best article of Vol 14 issue 20
A study by Sathyanarayanan AR et al. entitled \"The on-task Attention of Individuals with Autism Spectrum Disorder-An Eye Tracker Study Using Auticare\" is awarded Best article of Vol 14 issue 19
A study by Gupta P. et al. entitled \"A Short Review on \"A Novel Approach in Fast Dissolving Film & their Evaluation Studies\" is awarded Best Article of Vol 14 issue 18.
A study by Shafaque M. et al. entitled \"A Case-Control Study Performed in Karachi on Inflammatory Markers by Ciprofloxacin and CoAmoxicillin in Patients with Chronic Suppurative Otitis Media\" is awarded Best Article of Vol 14 issue 17
A study by Ali Nawaz et al. entitled \"A Comparative Study of Tubeless versus Standard Percutaneous Nephrolithotomy (PCNL) \? A Randomized Controlled Study\" is awarded Best Article for Vol 14 issue 16.
A study by Singh R. et al. entitled \"A Prospective Study to Find the Association of Astigmatism in Patients of Vernal Keratoconjunctivitis (VKC) in a Tertiary Health Care Centre in India (Vindhya Region MP)\" is awarded Best Article for Vol 14 issue 15
A Study by Humaira Tahir et al. entitled "Comparison of First Analgesic Demand after Major Surgeries of Obstetrics and Gynecology between Pre-Emptive Versus Intra-Operative Groups by Using Intravenous Paracetamol: A Cross-Sectional Study" is awarded Best Article for Vol 14 issue 14
A Study by Monica K. entitled "Risk Predictors for Lymphoma Development in Sjogren Syndrome - A Systematic Review" is awarded Best Article for Vol 14 issue 13
A Study by Mokhtar M Sh et al. entitled "Prevalence of Hospital Mortality of Critically Ill Elderly Patients" is awarded Best Article for Vol 14 issue 12
A Study by Vidya S. Bhat et al. entitled "Effect of an Indigenous Cleanser on the Microbial Biofilm on Acrylic Denture Base - A Pilot Study" is awarded Best Article for Vol 14 issue 11
A Study by Pandya S. et al. entitled "Acute and 28-Day Repeated Dose Subacute Toxicological Evaluation of Coroprotect Tablet in Rodents" is awarded Best Article for Vol 14 issue 10
A Study by Muhammad Zaki et al. entitled "Effect of Hemoglobin Level on the Severity of Acute Bronchiolitis in Children: A Case-Control Study" is awarded Best Article for Vol 14 issue 09
A Study by Vinita S & Ayushi S entitled "Role of Colour Doppler and Transvaginal Sonography for diagnosis of endometrial pathology in women presenting with Abnormal Uterine Bleeding" is awarded Best Article for Vol 14 issue 08
A Study by Prabhu A et al. entitled "Awareness of Common Eye Conditions among the ASHA (Accredited Social Health Activist) Workers in the Rural Communities of Udupi District- A Pilot Study" is awarded Best Article for Vol 14 issue 07
A Study by Divya MP et al. entitled "Non-Echoplanar Diffusion-Weighted Imaging and 3D Fiesta Magnetic Resonance Imaging Sequences with High Resolution Computed Tomography Temporal Bone in Assessment and Predicting the Outcome of Chronic Suppurative Otitis Media with Cholesteatoma" is awarded Best Article for Vol 14 issue 06
A Study by Zahoor Illahi Soomro et al. entitled "Functional Outcomes of Fracture Distal Radius after Fixation with Two Different Plates: A Retrospective Comparative Study" is awarded Best Article for Vol 14 issue 05
A Study by Ajai KG & Athira KN entitled "Patients’ Gratification Towards Service Delivery Among Government Hospitals with Particular Orientation Towards Primary Health Centres" is awarded Best Article for Vol 14 issue 04
A Study by Mbungu Mulaila AP et al. entitled "Ovarian Pregnancy in Kindu City, D.R. Congo - A Case Report" is awarded Best Article for Vol 14 issue 03
A Study by Maryam MJ et al. entitled "Evaluation Serum Chemerin and Visfatin Levels with Rheumatoid Arthritis: Possible Diagnostic Biomarkers" is awarded Best Article for Vol 14 issue 02
A Study by Shanthan KR et al. entitled "Comparison of Ultrasound Guided Versus Nerve Stimulator Guided Technique of Supraclavicular Brachial Plexus Block in Patients Undergoing Upper Limb Surgeries" is awarded Best Article for Vol 14 issue 01
A Study by Amol Sanap et al. entitled "The Outcome of Coxofemoral Bypass Using Cemented Bipolar Hemiarthroplasty in the Treatment of Unstable Intertrochanteric Fracture of Femur in a Rural Setup" is awarded Best Article Award of Vol 13 issue 24
A Study by Manoj KP et al. entitled "A Randomized Comparative Clinical Trial to Know the Efficacy of Ultrasound-Guided Transversus Abdominis Plane Block Against Multimodal Analgesia for Postoperative Analgesia Following Caesarean Section" is awarded Best Article Award of Vol 13 issue 23
A Study by Karimova II et al. entitled "Changes in the Activity of Intestinal Carbohydrases in Alloxan-Induced Diabetic Rats and Their Correction with Prenalon" is awarded Best Article of Vol 13 issue 22
A Study by Ashish B Roge et al. entitled "Development, Validation of RP-HPLC Method and GC MS Analysis of Desloratadine HCL and It’s Degradation Products" is awarded Best Article of Vol 13 issue 21
A Study by Isha Gaurav et al. entitled "Association of ABO Blood Group with Oral Cancer and Precancer – A Case-control Study" is awarded Best Article for Vol 13 issue 20
A Study by Amr Y. Zakaria et al. entitled "Single Nucleotide Polymorphisms of ATP-Binding Cassette Gene(ABCC3 rs4793665) affect High Dose Methotrexate-Induced Nephrotoxicity in Children with Osteosarcoma" is awarded Best Article for Vol 13 issue 19
A Study by Kholis Ernawati et al. entitled "The Utilization of Mobile-Based Information Technology in the Management of Dengue Fever in the Community Year 2019-2020: Systematic Review" is awarded Best Article for Vol 13 issue 18
A Study by Bhat Asifa et al. entitled "Efficacy of Modified Carbapenem Inactivation Method for Carbapenemase Detection and Comparative Evaluation with Polymerase Chain Reaction for the Identification of Carbapenemase Producing Klebsiella pneumonia Isolates" is awarded Best Article for Vol 13 issue 17
A Study by Gupta R. et al. entitled "A Clinical Study of Paediatric Tracheostomy: Our Experience in a Tertiary Care Hospital in North India" is awarded Best Article for Vol 13 issue 16
A Study by Chandran Anand et al. entitled "A Prospective Study on Assessment of Quality of Life of Patients Receiving Sorafenib for Hepatocellular Carcinoma" is awarded Best article for Vol 13 issue 15
A Study by Rosa PS et al. entitled "Emotional State Due to the Covid – 19 Pandemic in People Residing in a Vulnerable Area in North Lima" is awarded Best Article for Vol 13 issue 14
A Study by Suvarna Sunder J et al. entitled "Endodontic Revascularization of Necrotic Permanent Anterior Tooth with Platelet Rich Fibrin, Platelet Rich Plasma, and Blood Clot - A Comparative Study" is awarded Best Article for Vol 13 issue 13
A Study by Mona Isam Eldin Osman et al. entitled "Psychological Impact and Risk Factors of Sexual Abuse on Sudanese Children in Khartoum State" is awarded Best Article for Vol 13 issue 12
A Study by Khaw Ming Sheng & Sathiapriya Ramiah entitled "Web Based Suicide Prevention Application for Patients Suffering from Depression" is awarded Best Article for Vol 13 issue 11
A Study by Purushottam S. G. et al. entitled "Development of Fenofibrate Solid Dispersions for the Plausible Aqueous Solubility Augmentation of this BCS Class-II Drug" is awarded Best article for Vol 13 issue 10
A Study by Kumar S. et al. entitled "A Study on Clinical Spectrum, Laboratory Profile, Complications and Outcome of Pediatric Scrub Typhus Patients Admitted to an Intensive Care Unit from a Tertiary Care Hospital from Eastern India" is awarded Best Article for Vol 13 issue 09
A Study by Mardhiah Kamaruddin et al. entitled "The Pattern of Creatinine Clearance in Gestational and Chronic Hypertension Women from the Third Trimester to 12 Weeks Postpartum" is awarded Best Article for Vol 13 issue 08
A Study by Sarmila G. B. et al. entitled "Study to Compare the Efficacy of Orally Administered Melatonin and Clonidine for Attenuation of Hemodynamic Response During Laryngoscopy and Endotracheal Intubation in Gastrointestinal Surgeries" is awarded Best Article for Vol 13 issue 07
A Study by M. Muthu Uma Maheswari et al. entitled "A Study on C-reactive Protein and Liver Function Tests in Laboratory RT-PCR Positive Covid-19 Patients in a Tertiary Care Centre – A Retrospective Study" is awarded Best Article of Vol 13 issue 06 Special issue Modern approaches for diagnosis of COVID-19 and current status of awareness
A Study by Gainneos PD et al. entitled "A Comparative Evaluation of the Levels of Salivary IgA in HIV Affected Children and the Children of the General Population within the Age Group of 9 – 12 Years – A Cross-Sectional Study" is awarded Best Article of Vol 13 issue 05 Special issue on Recent Advances in Dentistry for better Oral Health
A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" is awarded Best Article of Vol 13 issue 06
A Study by Chen YY and Ghazali SRB entitled "Lifetime Trauma, posttraumatic stress disorder Symptoms and Early Adolescence Risk Factors for Poor Physical Health Outcome Among Malaysian Adolescents" is awarded Best Article of Vol 13 issue 04 Special issue on Current Updates in Plant Biology to Medicine to Healthcare Awareness in Malaysia
A Study by Kumari PM et al. entitled "Study to Evaluate the Adverse Drug Reactions in a Tertiary Care Teaching Hospital in Tamilnadu - A Cross-Sectional Study" is awarded Best Article for Vol 13 issue 05
A Study by Anu et al. entitled "Effectiveness of Cytological Scoring Systems for Evaluation of Breast Lesion Cytology with its Histopathological Correlation" is awarded Best Article of Vol 13 issue 04
A Study by Sharipov R. Kh. et al. entitled "Interaction of Correction of Lipid Peroxidation Disorders with Oxibral" is awarded Best Article of Vol 13 issue 03
A Study by Tarek Elwakil et al. entitled "Led Light Photobiomodulation Effect on Wound Healing Combined with Phenytoin in Mice Model" is awarded Best Article of Vol 13 issue 02
A Study by Mohita Ray et al. entitled "Accuracy of Intra-Operative Frozen Section Consultation of Gastrointestinal Biopsy Samples in Correlation with the Final Histopathological Diagnosis" is awarded Best Article for Vol 13 issue 01
A Study by Badritdinova MN et al. entitled "Peculiarities of a Pain in Patients with Ischemic Heart Disease in the Presence of Individual Combines of the Metabolic Syndrome" is awarded Best Article for Vol 12 issue 24
A Study by Sindhu Priya E S et al. entitled "Neuroprotective activity of Pyrazolone Derivatives Against Paraquat-induced Oxidative Stress and Locomotor Impairment in Drosophila melanogaster" is awarded Best Article for Vol 12 issue 23
A Study by Habiba Suhail et al. entitled "Effect of Majoon Murmakki in Dysmenorrhoea (Usre Tams): A Standard Controlled Clinical Study" is awarded Best Article for Vol 12 issue 22
A Study by Ghaffar UB et al. entitled "Correlation between Height and Foot Length in Saudi Population in Majmaah, Saudi Arabia" is awarded Best Article for Vol 12 issue 21
A Study by Siti Sarah Binti Maidin entitled "Sleep Well: Mobile Application to Address Sleeping Problems" is awarded Best Article for Vol 12 issue 20
A Study by Avijit Singh"Comparison of Post Operative Clinical Outcomes Between “Made in India” TTK Chitra Mechanical Heart Valve Versus St Jude Mechanical Heart Valve in Valve Replacement Surgery" is awarded Best Article for Vol 12 issue 19
A Study by Sonali Banerjee and Mary Mathews N. entitled "Exploring Quality of Life and Perceived Experiences Among Couples Undergoing Fertility Treatment in Western India: A Mixed Methodology" is awarded Best Article for Vol 12 issue 18
A Study by Jabbar Desai et al. entitled "Prevalence of Obstructive Airway Disease in Patients with Ischemic Heart Disease and Hypertension" is awarded Best Article for Vol 12 issue 17
A Study by Juna Byun et al. entitled "Study on Difference in Coronavirus-19 Related Anxiety between Face-to-face and Non-face-to-face Classes among University Students in South Korea" is awarded Best Article for Vol 12 issue 16
A Study by Sudha Ramachandra & Vinay Chavan entitled "Enhanced-Hybrid-Age Layered Population Structure (E-Hybrid-ALPS): A Genetic Algorithm with Adaptive Crossover for Molecular Docking Studies of Drug Discovery Process" is awarded Best article for Vol 12 issue 15
A Study by Varsha M. Shindhe et al. entitled "A Study on Effect of Smokeless Tobacco on Pulmonary Function Tests in Class IV Workers of USM-KLE (Universiti Sains Malaysia-Karnataka Lingayat Education Society) International Medical Programme, Belagavi" is awarded Best article of Vol 12 issue 14, July 2020
A study by Amruta Choudhary et al. entitled "Family Planning Knowledge, Attitude and Practice Among Women of Reproductive Age from Rural Area of Central India" is awarded Best Article for special issue "Modern Therapeutics Applications"
A study by Raunak Das entitled "Study of Cardiovascular Dysfunctions in Interstitial Lung Diseas epatients by Correlating the Levels of Serum NT PRO BNP and Microalbuminuria (Biomarkers of Cardiovascular Dysfunction) with Echocardiographic, Bronchoscopic and HighResolution Computed Tomography Findings of These ILD Patients" is awarded Best Article of Vol 12 issue 13 
A Study by Kannamani Ramasamy et al. entitled "COVID-19 Situation at Chennai City – Forecasting for the Better Pandemic Management" is awarded best article for  Vol 12 issue 12
A Study by Muhammet Lutfi SELCUK and Fatma entitled "Distinction of Gray and White Matter for Some Histological Staining Methods in New Zealand Rabbit's Brain" is awarded best article for  Vol 12 issue 11
A Study by Anamul Haq et al. entitled "Etiology of Abnormal Uterine Bleeding in Adolescents – Emphasis Upon Polycystic Ovarian Syndrome" is awarded best article for  Vol 12 issue 10
A Study by entitled "Estimation of Reference Interval of Serum Progesterone During Three Trimesters of Normal Pregnancy in a Tertiary Care Hospital of Kolkata" is awarded best article for  Vol 12 issue 09
A Study by Ilona Gracie De Souza & Pavan Kumar G. entitled "Effect of Releasing Myofascial Chain in Patients with Patellofemoral Pain Syndrome - A Randomized Clinical Trial" is awarded best article for  Vol 12 issue 08
A Study by Virendra Atam et. al. entitled "Clinical Profile and Short - Term Mortality Predictors in Acute Stroke with Emphasis on Stress Hyperglycemia and THRIVE Score : An Observational Study" is awarded best article for  Vol 12 issue 07
A Study by K. Krupashree et. al. entitled "Protective Effects of Picrorhizakurroa Against Fumonisin B1 Induced Hepatotoxicity in Mice" is awarded best article for issue Vol 10 issue 20
A study by Mithun K.P. et al "Larvicidal Activity of Crude Solanum Nigrum Leaf and Berries Extract Against Dengue Vector-Aedesaegypti" is awarded Best Article for Vol 10 issue 14 of IJCRR
A study by Asha Menon "Women in Child Care and Early Education: Truly Nontraditional Work" is awarded Best Article for Vol 10 issue 13
A study by Deep J. M. "Prevalence of Molar-Incisor Hypomineralization in 7-13 Years Old Children of Biratnagar, Nepal: A Cross Sectional Study" is awarded Best Article for Vol 10 issue 11 of IJCRR
A review by Chitra et al to analyse relation between Obesity and Type 2 diabetes is awarded 'Best Article' for Vol 10 issue 10 by IJCRR. 
A study by Karanpreet et al "Pregnancy Induced Hypertension: A Study on Its Multisystem Involvement" is given Best Paper Award for Vol 10 issue 09

List of Awardees

A Study by Ese Anibor et al. "Evaluation of Temporomandibular Joint Disorders Among Delta State University Students in Abraka, Nigeria" from Vol 13 issue 16 received Emerging Researcher Award


A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" from Vol 13 issue 06 received Emerging Researcher Award


RSS feed

Indexed and Abstracted in


Antiplagiarism Policy: IJCRR strongly condemn and discourage practice of plagiarism. All received manuscripts have to pass through "Plagiarism Detection Software" test before Toto Macau forwarding for peer review. We consider "Plagiarism is a crime"

IJCRR Code of Conduct: To achieve a high standard of publication, we adopt Good Publishing Practices (updated in 2022) which are inspired by guidelines provided by Committee on Publication Ethics (COPE), Open Access Scholarly Publishers Association (OASPA) and International Committee of Medical Journal Editors (ICMJE)

Disclaimer: International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal.



ABOUT US

International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal

Contact

148, IMSR Building, Ayurvedic Layout,
        Near NIT Complex, Sakkardara,
        Nagpur-24, Maharashtra State, India

editor@ijcrr.com

editor.ijcrr@gmail.com


Copyright © 2024 IJCRR. Specialized online journals by ubijournal .Website by Ubitech solutions