SYNTHESIS, CHARACTERIZATION AND ANTIMICROBIAL ACTIVITY OF SOME NOVEL 3,4-DISUBSTITUTED PYRAZOLE DERIVATIVES
Objective: The objective of the current work was to synthesize a series of 3,4-substituted pyrazoles from the cyclization of substituted aryl ethanone and hydrazine hydrate in a two-step process and screen the derivatives for their antimicrobial activity.
Methods: The title compounds were derived from the condensation of ethanone intermediate with N, N-Dimethyl formamide-dimethyl acetal and hydrazine hydrate. Ethanone intermediate synthesized from substituted methyl phenylacetate in the presence of potassium t-butoxide with 6-methyl pyridine-2-carboxylic acid methyl ester.
Results: The final products were characterized by detailed spectral analysis using Mass, Nuclear Magnetic Resonance, and Infra Red spectroscopy. All the compounds (4a-4j) showed significant antibacterial properties on both Gram-positive and Gram-negative bacteria. Interestingly, the selected microbes were found to be highly sensitive for compound 4a, 4c, 4d, 4h, and 4i. The molecules are also antifungal in nature, and they have a significant inhibitory effect on the growth of Candida albicans and Aspergillus niger.
Conclusion: The results suggest that the developed derivatives bearing the pyrazole nucleus could be the lead structures for the development of antimicrobial agents for fatal infections.
2. el-Moghazy SM, Barsoum FF, Abdel-Rahman HM, Marzouk A. Synthesis and anti-inflammatory activity of some pyrazole derivatives. Med Chem Res 2012;21:1722-33.
3. Kumar RS, Arif IA, Ahamed A, Idhayadhulla A. Anti-inflammatory and antimicrobial activities of novel pyrazole analogues. Saudi J. Bio Sci 2016;23:614-20.
4. Ardiansah B. Recent reports on pyrazole-based bioactive compounds as candidate for anticancer agents. Asian J Pharm Clin Res 2017;10:45-51.
5. Mahaveer P, Kulkarni RG, Radakrishna P, Chandrashekar VM, Achaiah G. Synthesis, characterization and anti-inflammatory activity of novel pyrazolyl ketoamides. Indian J Chem 2013;52:818-23.
6. Rahimizadeh M, Pordel M, Bakavoli M, Rezaeian S, Sadeghian A. Synthesis and antibacterial activity of some new derivatives of pyrazole. World J Microbiol Biotechnol 2010;26:317-21.
7. Sharma KP, Sharma HK. Some hexa-coordinated lanthanide (III) iodide complexes with schiff bases of cyanoethylated benzaldehyde. Asian J Chem 2007;19:4129-34.
8. Bhaskar VH, More VS, Kumar M. Biological activities of 4-(substitued phenyl)-5-(2,4- dinitrophenyl)-3-methyl-1,3a,4,5-tetrahydropyrazolo-[3,4-c] pyrazole. Asian J Chem 2008;20:5474-85.
9. Solanki PR, Wadodkar KN, Rai MK, Wagh P. Synthesis and biological evaluation of some tri- and tetra-substituted pyrazoles and isoxazoles. Asian J Chem 2003;15:1864-73.
10. Janus SL, Magdif AZ, Erik BP, Claus N. Synthesis of triazenopyrazole derivatives as potential inhibitors of HIV-1. Monatsh Chem 1999;130:1167-74.
11. el-Sabbagh OI, Baraka MM, Ibrahim SM, Pannecouque C, Andrei G, Snoeck R, et al. Synthesis and antiviral activity of new pyrazole and thiazole derivatives. Eur J Med Chem 2009;44:3746-54.
12. Bekhit AA, Hymete A, Asfaw H, Bekhit AE. Evaluation of some 1H-pyrazole derivatives as a dual acting antimalarial and anti Leishmania agent. Arch Pharm Med Chem 2012;345:147-52.
13. Vaidya AB, Morrisey JM, Zhang W, Das S, Daly TM, et al. Pyrazoleamide compounds are potent antimalarials that target Na+ homeostasis in intraerythrocytic Plasmodium falciparum. Nat Commun 2014;5:5521-30.
14. Gawad NM, Hassan GS, Georgy HH. Review: Biologically active pyrazole derivatives. Med Chem Res 2012;21:983-94.
15. Selvam TP, Kumar PV, Saravanan G, Prakash CR. Microwave-assisted synthesis, characterization and biological activity of novel pyrazole derivatives. J Saudi Chem Soc 2014;18:1015-21.
16. Jayanna ND, Vagdevi HM, Dharshan JC, Raghavendra R, Telkar SB. Synthesis, antimicrobial, analgesic activity, and molecular docking studies of novel 1-(5,7-dichloro-1,3-benzoxazol-2-yl)-3-phenyl-1H-pyrazole-4-carbaldehyde. Med Chem Res 2013;22:5814-22.
17. Malvar D, Ferreira RT, de Castro RA, de Castro LL, Freitas AA, Costa EA, et al. Antinociceptive, anti-inflammatory and antipyretic effects of 1.5-diphenyl-1H-Pyrazole-3-carbohydrazide, a new heterocyclic pyrazole derivative. Life Sci 2014;95:81-8.
18. Menozzi G, Mosti L, Schenone P, D’Amico M, Filippelli A, Rossi F. 4H-thieno[3,4- c]pyrazole derivates with antiinflammatory, analgesic, antipyretic and platelet antiaggregating activities. Farmaco 1992;47:1495-511.
19. Geha RM, Chen K, Wouters J, Ooms F, Shih J. Analysis of conserved active site residues in monoamine oxidase A and B and their three-dimensional molecular modeling. J Biol Chem 2002;277:17209-16.
20. Foley P, Gerlach M, Youdim MB, Riederer P. MAO-B inhibitors: Multiple roles in the therapy of neurodegenerative disorders? Parkinsonism Relat Disord 2008;6:25-47.
21. Palaska E, Aydin F, Ucar G, Erol D. Synthesis and screening of human monoamine oxidase-a inhibitor effect of new 2-pyrazoline and hydrazone derivatives. Arch Pharm Chem Life Sci 2008;341:209-17.
22. Aragade P, Sadhana K, Hemant K, Dwarkadas B, Veeresh M. Synthesis, anti-inflammatory, analgesic and antipyretic activity of novel 1,3,5-trisubstituted pyrazole derivatives. Int J Drug Des Discov 2012;3:688-78.
23. Alagarsamy V, Saravanan G. Synthesis and anticonvulsant activity of novel quinazolin-4 (3H)-one derived pyrazole analogs. Med Chem Res 2013;22:1711-22.
24. Gurunanjappa P, Nagamallu R, Kariyappa AK. Synthesis and antimicrobial activity of novel fused pyrazoles. Int J Pharm Pharm Sci 2014;7:379-81.
25. Kumar DS, Suresh K. Synthesis and in vitro antifungal activity of chalcone derivatives linked with 1, 2, 4 triazole. Asia J pharm Anal Med Chem 2017;5:60-4.
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