Abstract
Fourteen newly synthesized derivatives of indophenazine 1,3,5-trisubstituted pyrazoline bearing benzofuran were prepared from benzofuran chalcones with indophenazine hydrazide through cycloaddition reaction. All the compounds were screened for their in vitro and in vivo antitubercular activity against drug resistant and multidrug-resistant Mycobacterium tuberculosis H37RV. The MIC50 and MIC90 were estimated and compared with rifampicin and gatifloxacin standard drugs. Nitro group containing at ortho 5j, meta 5e, furan ring containing 5m and ortho 5i, para 5h chloro containing compounds were exhibited significant in vitro, in vivo antitubercular activity against standard drugs.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Agrawal YK, Manna K, Babu VH, Srinivasan KK, Bhatt H, Gogoi PJ (2007) Synthesis and biological evaluations of new benzofuran 1, 3, 5-trisubstitued pyrazoline derivatives of paracetamol as potential antitubercular, antimicrobial agents. Indian J Heterocycl Chem 16:263–266
Albalak R, O’Brien RJ, Kammerer JS, O’Brien SM, Marks SM, Castro KG, Moore M (2007) Trends in tuberculosis/human immunodeficiency virus comorbidity, United States, 1993–2004. Arch Intern Med 167:2443–2452
Ali MA, Shaharyar M, Siddiqui AA (2007) Synthesis, structural activity relationship and anti-tubercular activity of novel pyrazoline derivatives. Eur J Med Chem 42:268–275
Bryson L, Szybalski W (1952) Microbial selection. Science 116:45–51
Collins L, Franzblau SG (1997) Microplate alamar blue assay versus BACTEC 460 system for high throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium avium. Antimicrob Agents Chemother 41:1004–1009
Corbett EL, Watt CJ, Walker N, Maher D, Williams BG, Raviglione MC, Dye C (2003) The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. Arch Intern Med 163:1009–1021
Gundersen LL, Meyer JM, Spilsberg B (2002) Synthesis and antimycobacterial activity of 6-arylpurines: the requirements for the N-9 substituent in active antimycobacterial purines. J Med Chem 45:1383–1386
Husain K, Abid M, Azam A (2008) Novel Pd(II) complexes of 1-N-substituted 3-phenyl-2-pyrazoline derivatives and evaluation of antiamoebic activity. Eur J Med Chem 43:393–403
Interleid B (1991) In: Lorian V (ed) Antibiotic in laboratory medicine, 3rd edn. Williams and Wilkins, Baltimore, p 134
Kini SG, Bhat AR, Bryant B, Williamson JS, Dayan FE (2009) Synthesis, antitubercular activity and docking study of novel cyclic azole substituted diphenyl ether derivatives. Eur J Med Chem 44:492–500
Kirilmis C, Ahmedzade M, Servi S, Koca M, Kizirgil A, Kazaz C (2008) Synthesis and antimicrobial activity of some novel derivatives of benzofuran. Part 2. The synthesis and antimicrobial activity of some novel 1-(1-benzofuran-2-yl)-2-mesitylethanone derivatives. Eur J Med Chem 43:300–308
Lenaerts AJ, Gruppo V, Marietta KS, Johnson CM, Driscoll DK, Tompkins NM, Rose JD, Reynolds RC, Orme IM (2005) Preclinical testing of the nitroimidazopyran PA-824 for activity against Mycobacterium tuberculosis in a series of in vitro and in vivo models. Antimicrob Agents Chemother 49:2294–2301
Lenaerts AJ, Bitting C, Woolhisher L, Gruppo V, Marietta KS, Johnson CM, Orme IM (2008) Evaluation of a 2-pyridone, KRQ-10018, against Mycobacterium tuberculosis in vitro and in vivo. Antimicrob Agents Chemother 52:1513–1515
Manna K, Agrawal YK (2009) Microwave assisted synthesis of new indophenazine 1,3,5-trisubstituted pyrazoline derivatives of benzofuran and their antimicrobial activity. Bioorg Med Chem Lett 19:2688–2692
Manna K, Babu VH, Srinivasan KK, Sneha J, Bhatt GV (2004) Synthesis and biological evaluation of 1,3,5-trisubstituted pyrazolines bearing benzofuran. Indian J Heterocycl Chem 13:253–256
Manna K, Agrawal YK, Srinivasan KK (2008) Synthesis and biological evaluations of new benzofuran isoxazole derivatives as potential antitubercular, antibacterial and antifungal agents. Indian J Heterocycl Chem 17:250–252
Mustafa J, Khan SI, Ma G, Walker LA, Khan IA (2005) Synthesis and in vitro cytotoxic activity of N-, F-, and S-ether derivatives of podophyllotoxin fatty acid adducts. Lipids 40:375–382
Prakash O, Kumar R, Prakash V (2008) Synthesis and antifungal activity of some new 3-hydroxy-2-(1-phenyl-3-aryl-4-pyrazolyl) chromones. Eur J Med Chem 43:435–440
Sriram D, Yogeeswari P, Basha SJ (2005) Synthesis and antimycobacterial evaluation of various 7-substituted ciprofloxacin derivatives. Bioorg Med Chem 13:5774–5778
Sriram D, Senthil PK, Dinakaran M, Yogeeswari P, China A, Nagaraja V (2007) Antimycobacterial activities of novel 1-(cyclopropyl/tert-butyl/4-fluorophenyl)-1,4-dihydro-6-nitro-4-oxo-7-(substituted secondary amino)-1,8-naphthyridine-3-carboxylic acid. J Med Chem 50:6232–6239
Stover CK, Warrener P, VanDevanter DR, Sherman DR, Arain TM, Langhorne MH, Anderson SW, Towell JA, Yuan Y, McMurray DN, Kreiswirth BN, Barry CE, Baker WR (2000) A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis. Nature 405:962–966
Tanoue S, Mitarai S, Shishido H (2002) Comparative study on the use of solid media: Löwenstein–Jensen and Ogawa in the determination of anti-tuberculosis drug susceptibility. Tuberculosis 82:63–67
Trias J, Benz R (1993) Permeability of the cell wall of Mycobacterium smegmatis. Mol Microbiol 14:283–290
Tyagi S, Nuermberger E, Yoshimatsu T, Williams K, Rosenthal I, Lounis N, Bishai W, Grosset J (2005) Bactericidal activity of the nitroimidazopyran PA-824 in a murine model of tuberculosis. Antimicrob Agents Chemother 49:2289–2293
Acknowledgments
The authors gratefully acknowledge to Department of Microbiology, Kasturba Medical College, Manipal, India for providing laboratory facilities to carryover the in vivo and in vitro antitubercular activity. We acknowledge to IISc, Bangalore, SPIC Foundation, Chennai and Tuberculosis Research Centre (Chennai, India) for provided 1H NMR spectra, mass spectra, elemental analysis, and MDR-TB stain, respectively. Authors heartily acknowledge to Nirma University, Ahmedabad, Gujarat, India for the financial support, laboratory facilities, and other requirements.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Manna, K., Agrawal, Y.K. Potent in vitro and in vivo antitubercular activity of certain newly synthesized indophenazine 1,3,5-trisubstituted pyrazoline derivatives bearing benzofuran. Med Chem Res 20, 300–306 (2011). https://doi.org/10.1007/s00044-010-9322-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00044-010-9322-5