SYNTHESIS OF INDOLE, COUMARINYL AND PYRIDINYL DERIVATIVES OF ISONIAZID AS POTENT ANTITUBERCULAR AND ANTIMICROBIAL AGENTS AND THEIR MOLECULAR DOCKING STUDIES


Anil S. Rathod, Shivakumar S. Godipurge, Jaiprakash S. Biradar

Abstract


Objective: The aim of this study was to the synthesis of indole, coumarinyl and pyridinyl derivatives of isoniazid as potent anti-TB and antimicrobial agents and their molecular docking studies.

Methods: The structures of the newly synthesized compounds were confirmed by FT-IR, 1HNMR, and Mass spectroscopic methods and to evaluate the biological studies like anti-TB, antimicrobial and antioxidant activities. The mode of action of these active compounds was carried out by molecular docking studies.

Results: Among all the synthesized compounds tested 5d was found to be the most active with M. tuberculosis H37Rv strain at 12.5µg/ml, 5b at 25µg/ml, 4d was found to be the most active with S. typhi, S. aureus and A. Nizer, 5a with A. Oryzae, 5c with A. terrous and A. Flavous and 5d with Shegella at 100µg/ml and some of the compounds like 4d, 5a, 5b and 5d have shown promising antioxidant properties.

Conclusion: All the synthesized compounds have exhibited promising anti-TB, antimicrobial and antioxidant activities. 


Keywords


Indole, Coumarin, Isonicotinic acid hydrazide[INH], Pyrazole, M.tuberculosis, Antimicrobial , Antioxidant activities and Molecular Docking Studies.

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References


Collins FM. Mycobacterial disease, immune suppression and acquired immunodeficiency syndrome. Clin Microbiol Rev 1989;2:360-77.

Graham NM, Galai KE, Nelson J. Effect of isoniazid chemoprophylaxis on the HIV-related mycobacterial disease. Arch Intern Med 1996;156:889-94.

Halsey NA, Coberly JS, Desormeaux J, Losikoff P. Randomised trial of isoniazid versus rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1 infection. Lancet 1998; 351:786-92.

Inderlied CB, Kemper CA, Bermudez LE. The mycobacterium avium complex. Clin Microbiol Rev 1993;6:266-10.

Telzak EE, Sepkowitz K, Alpert P. Multidrug-resistant tuberculosis in patients without HIV infection. N Engl J Med 1995;333:907-11.

Dessen AA, Quemard JS, Blanchard WR, Sacchettini JC. Crystal structure and function of the isoniazid target of M. tuberculosis. Science 1995;267:1638-41.

Morris S, Bai GH, Suffys P, Portilo-Gomez L. Molecular mechanisms of multiple drug resistance in clinical isolates of Mycobacterium tuberculosis. J Infect Dis 1995;171:954-60.

Mandell GL, Petri WA. Antimicrobial agents used in the chemotherapy of tuberculosis. In: Hardman J. eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 9th edn. McGraw-Hill, New York; 1996. p. 1155-74.

Sensi P, Grassi G. Antimycobacterial agents. In: Wolff ME. Ed. Burger’s medicinal chemistry and drug discovery. 5th edn. Wiley, New York; 1996. p. 575-35.

Kucukguzel SG, Rollas S. Synthesis, characterization and pharmacological properties of some 4 arylhydrazono-2-pyrazoline-5-one derivatives obtained from heterocyclic amines. Eur J Med Chem 2000;35:761-5.

Nauduri D, Reddy GB. Antibacterials and antimycotics. Part 1. Synthesis and activity of 2 pyrazoline derivatives. Chem Pharm Bull 1998;46:1254-7.

Ali MA, Shaharyar M, Siddiqui AA. Synthesis, structural activity relationship and anti-tubercular activity of novel pyrazoline derivatives. Eur J Med Chem 2007;42:268-75.

Shaharyar M, Siddiqui AA, Ali MA. Synthesis and in vitro antimycobacterial activity of N1-nicotinoyl-3-(40-hydroxy-30-methyl phenyl)-5-[(sub)phenyl]-2-pyrazolines. Bioorg Med Chem Lett 2006a;16:3947-52.

Shaharyar M, Siddiqui AA, Ali MA. Synthesis and evaluation of phenoxy acetic acid derivatives as an anti-mycobacterial agent. Bioorg Med Chem Lett 2006b;16:4571-8.

Genin MJ, Allwine DA, Anderson DJ. Substituent effects on the antibacterial activity of nitrogen–carbon-linked (azolylphenyl) oxazolidinones with expanded activity against the fastidious gram-negative organisms H. influenzae and M. catarrhalis. J Med Chem 2000;43:953-70.

Kucukguzel SG, Rollas S. Synthesis, characterization of novel coupling products and 4 arylhydrazono-2-pyrazoline-5-ones as potential antimycobacterial agents. IL Farmaco 2002;57:583-7.

Shenoy GG, Bhat AR, Bhat GV, Kotian M. Synthesis of pyrazoles and isoxazole in triethanolamine medium. Indian J Heterocycl Chem 2001;10:197-9.

Kopec AE, Zwolska Z. Bioavailability factors of INH in fast and slow acetylators, healthy volunteers. Acta Poloniae Pharm 2002;59:452-7.

Aragade, Mahesh P, Pradeepkumar R. Coumarinyl pyrazole derivatives of INH: promising antimycobacterial agents. Med Chem Res 2013;22:2279-83.

Aragade P, Maddi V, Khode S. Synthesis and antibacterial activity of new series of 3-[3(substituted phenyl)-1-isonicotinoyl-1H-pyrazol-5-yl]-2H-chromen-2-one derivatives. Arch Pharm Chem Life Sci 2009;342:361-6.

Doddappa A, Biradar JS. Synthesis of novel substituted pyrazolines and isoxazolines containing indole and coumarines. Heterocycl Commun 2009;6:411-16.

Biradar JS. Studies in the indole field. Ph. D. Thesis, Gulbarga University; 1982.

Knoevenagel E. Condensationn zwischen malonester und aldehyden unter dem einfluss von ammoniak und organischen aminen. Chem Ber 1898;31:2596.

Maria CS, Lourenco, Marcus V, deSouza N. Evaluation of anti-tubercular activity of nicotinic and isoniazid analogues. ARKIVOC 2007;15:181-91.

Godipurge SS, Yallappa S, Biradar NJ, Biradara JS. A facile and green strategy for the synthesis of Au, Ag and Au-Ag alloy nanoparticles using aerial parts of R. hypocrateriformis extract and their biological evaluation. Enzyme Microbial Technol 2016;95:174-84.

Biradar JS, Sashidhar BS, Parveen R. Synthesis, antioxidant and DNA cleavage activities of novel indole derivatives. Eur J Med Chem 2010;45:4074-8.

Godipurge SS, Rahber S, Biradar JS, Mahurkar N. Evaluation of pharmacological activities of Rivea hypocrateriformis in experimental animal models. Inter J Toxicol Pharmacol Res 2015;7:65-73.

Godipurge SS, Biradar NJ, Biradar JS, Mahurkar N. Chemical composition and hepatoprotective effects of polyphenolic fraction from Rivea hypocrateriformis in paracetamol-induced liver damage in wistar albino rats. Int J Pharm Pharm Sci 2016;8:228-34.

Biradar JS, Sashidhar BS. Design and synthesis of some novel thiophene analogues of indole as a potent antimicrobial and antioxidant agents. Org Chem 2010;4:280-3.

Biradar JS, Sashidhar BS, Parveen R. Synthesis, antioxidant and DNA cleavage activities of novel indole derivatives. Eur J Med Chem 2010;45:4074-8.

Biradar JS, Sasidhar BS. Solvent-free, microwave assisted Knoevenagel condensation of novel 2, 5-disubstituted indole analogues and their biological evaluation. Eur J Med Chem 2011;46:6112–8.

Javarappa R, Nagaraja N. Synthesis and screening of benzofuran fused C-2,4,6-substituted pyrimidine derivatives as a new antibacterial and antifungal agent. Int J Pharm Pharm Sci 2017;9:27-32.




About this article

Title

SYNTHESIS OF INDOLE, COUMARINYL AND PYRIDINYL DERIVATIVES OF ISONIAZID AS POTENT ANTITUBERCULAR AND ANTIMICROBIAL AGENTS AND THEIR MOLECULAR DOCKING STUDIES

Keywords

Indole, Coumarin, Isonicotinic acid hydrazide[INH], Pyrazole, M.tuberculosis, Antimicrobial , Antioxidant activities and Molecular Docking Studies.

DOI

10.22159/ijpps.2017v9i12.21970

Date

01-12-2017

Additional Links

Manuscript Submission

Journal

International Journal of Pharmacy and Pharmaceutical Sciences
Vol 9, Issue 12, 2017 Page: 233-240

Online ISSN

0975-1491

Statistics

34 Views | 7 Downloads

Authors & Affiliations

Anil S. Rathod
Department of Chemistry, Gulbarga University, Kalaburagi 585106
India

Shivakumar S. Godipurge
Department of Chemistry, Gulbarga University, Kalaburagi 585106

Jaiprakash S. Biradar
Department of Chemistry, Gulbarga University, Kalaburagi 585106


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