PYRIMIDINE INCORPORATED SCHIFF BASE OF ISONIAZID WITH THEIR SYNTHESIS, CHARACTERIZATION AND IN VITRO BIOLOGICAL EVALUATION
Â Objective: Versatile biological activities of nitrogen containing heterocycles in medicinal chemistry, mainly pyrimidine and pyridine ring based heterocyclic moieties are very important. Pharmaceutical important of pyrimidine and isoniazid moiety prompted us to synthesize isoniazid clubbed pyrimidine derivatives and evaluated for antimicrobial and antituberculosis activity.
Method: 2-(2-(3-bromo benzylidene)-1-isonicotinoyl hydrazinyl)-N-(4-(substituted phenyl)-6-(substituted aryl) pyrimidin-2-yl) acetamide 2(A-J) have been synthesized by condensation reaction of 2-chloro-N-[4-(substituted phenyl)-6-(substituted aryl) pyrimidin-2-yl] acetamide and Nâ€™-[(E)- (3-bromophenyl) methylidene]pyridine-4-carbohydrazide. All newly synthesized compounds were screened for in vitro antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus pyogenes, antifungal against Candida albicans, Aspergillus niger, and Aspergillus clavatus, and antituberculosis activity against Mycobacterium tuberculosis H37RV.
Results: Majority of the compounds exhibited good antibacterial, antifungal, and antituberculosis activity. All titled compounds were characterized by spectral analyses (infrared spectroscopy, nuclear magnetic resonance spectroscopy, and mass spectroscopy).
Conclusion: 2-(2-(3-bromo benzylidene)-1-isonicotinoyl hydrazinyl)-N-(4-(substituted phenyl)-6-(substituted aryl) pyrimidin-2-yl) acetamide 2(A-J) showed good antimicrobial activity and comparatively good antituberculosis activity. Hence, all the compounds of this series considered for future investigation mainly in area of antibacterial, antifungal study.
2. LourenÃ§o MC, De Souza MV, Pinheiro AC, Ferreira ML, GonÃ§alves RS, Nogueira TC. Evaluation of anti-tubercular activity of nicotinic and isoniazid analogues. Arkivoc 2007;15:181-91.
3. Thomas B, Harindran J. Design, synthesis and evaluation of anti tubercular activity of amino a zetidinones from isoniazid. Int J Phrm Sci Res 2016;7(7):2795-804.
4. Kachroo M, Panda R, Yadav Y. Synthesis and biological activities of some new pyrimidine derivatives from chalcones. Pharm Chem 2014;6(2):352-9.
5. Patel PN, Karia DC. Synthesis and bioactivity evaluation of novel bipyenylthioxo-pyrimidines as potent antimicrobial agent. Pharm Chem 2015;7(10):427-33.
6. Kumaresan S, Chandrasekaran S, Sakthivel KM, Guruvayoorappan C, Enoch IV. Synthesis, characterization and anti-inflammatory activity of some novel pyrimidin-2-amines on carrageenan-induced paw edema in balb/c mice. J Chem Pharm Res 2014;6(10):593-606.
7. Bano T, Kumar N, Dudhe R. Free radical scavenging properties of pyrimidine derivatives. Org Med Chem Lett 2012;2(1):34.
8. Mohana KN, Basavapatna N, Kumar P, Mallesha L. Synthesis and biological activity of some pyrimidine derivatives. Drug Invent Today 2013;5(3):216-22.
9. Kaur N, Aggarwal AK, Sharma N, Choudhary B. Synthesis and in-vitro antimicrobial activity of pyrimidine derivatives. Int J Pharm Sci Drug Res 2012;4(3):199-204.
10. Punkvang A, Saparpakorn P, Hannongbua S, Wolschann P, Pungpo P. Elucidating drug-enzyme interactions and their structural basis for improving the affinity and potency of isoniazid and its derivatives based on computer modeling approaches. Molecules 2010;15(4):2791-813.
11. Sahu S, Siddiqui N. A review on biological importance of pyrimidines in the New Era. Int J Pharm Pharm Sci 2016;8(5):8-21.
12. Kaur R, Kaur P, Sharma S, Singh G, Mehndiratta S, Bedi PM, et al. Anti-cancer pyrimidines in diverse scaffolds: A review of patent literature. Recent Pat Anticancer Drug Discov 2015;10(1):23-71.
13. Phoujdar MS, Aland GR. Molecular docking study on 1H-(3,4d) pyrazolo-pyrimidines as cyclin dependant kinase (cdk2) inhibitors. Int J Curr Pharm Res 2017;9(1):94-100.
14. David VB, Babu VH, Reddy BM. Synthesis of novel 4,6-disubstituted-2-amino pyrimidines as antibacterial agents. Int J Pharm Chem Res 2014;3(14):1-6.
15. Patel NB, Patel HR. Design and synthesis of new imidazolinone derivatives as a potential anti fungal agents. J Heterocycl Chem 2011;48:373-80.
16. Patel NB, Patel HR. Synthesis and pharmacological studies of 5-ethylpyridin-2-ethanol analogs derivatives. Arkivok 2009;12:302-21.
17. Patel NB, Patel HR. Design and synthesis of 2-(5-ethyl-pyridine-2-yl)ethanol analogs as potential microbial agents. Int J Drug Des Discov 2010;1(1):93-106.
18. Agarwal A, Kumar B, Mehrotra PK, Chauhan PM. 2,4,6-trisubstituted pyrimidine derivatives as pregnancy interceptive agents. Bioorg Med Chem 2005;13(6):1893-9.
19. Sunduru N, Agarwal A, Katiyar SB, Nishi, Goyal N, Gupta S, et al. Synthesis of 2,4,6-trisubstituted pyrimidine and triazine heterocycles as antileishmanial agents. Bioorg Med Chem 2006;14(23):7706-15.
20. Badavath VN, Sinha BN, Jayaprakash V. Design, in-silico docking and predictive ADME properties of novel pyrazoline derivatives with selective human MAO inhibitory activity. Int J Pharm Pharm Sci 2015;7(12):277-82.
21. Rammohan P, Taradas S, Tapas S. Improved microwave-induced synthesis of indolylchalcones. Arch Appl Sci Res 2014;6(3):138-41.
22. Mathew B, Unnikirishnan G, Shafeer VP, Mohammed MC, Femina P. Microwave assisted synthesis, physicochemical properties and antimicrobial activity of benzimidazole chalcones. Pharm Chem 2011;3(6):627-31.
23. Revathi R, Sree CR, Jayakumar R, Visagaperumal D, Anbalagan N. Microwave assisted synthesis and biological activity of certain 4-hydroxy chalcones. Pharmacophore 2013;4(2):59-69.
24. Sweta S, Choudhary PC, Intodia K. Microwave irradiation synthesis of various substituted chalcones using various heterogeneous catalysts under solvent-free conditions and their biological study. Chem Sci Trans 2013;2(2):343-8.
25. Karthikeyan E, Mohammed AA, Manogaran E, Kalpana E, Sivaneswari S, Kumar MS, et al. Design, synthesis and biological evaluation of some novel isoniazid cyclocondensed azitidinone. Drug Invent Today 2013;5:100-4.
26. Nalini CN, Arivukkarasi, Devi R. Structure based drug design, synthesis, characterization and biological evaluation of novel isoniazid derivatives. Rasayan J Chem 2011;4(4):868-74.
27. Rattan A, Churchill BI. Antimicrobials in Laboratory Medicine. New Delhi: Livingstone; 2000. p. 85.
28. Anargyros P, Astill DS, Lim IS. Comparison of improved BACTEC and Lowenstein-Jensen media for culture of mycobacteria from clinical specimens. J Clin Microbiol 1990;28(6):1288-91.
29. The National Committee for Clinical Laboratory Standard. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts Approved Standard M27A. Wayne, PA: NCCLS; 1997.
30. Robert C. Medical Microbiology. 11th ed. Briton: ELBS and E & S., Livingstone; 1970. p. 89.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.