Abstract
A series of 2-(substituted-phenyl)-3-(((3-(pyridin-4-yl)-1-(p-tolyl)-1H-pyrazol-4-yl)methylene)amino)-quinazolin-4(3H)-ones have been synthesized. The structures of the synthesized compounds were assigned on the basis of IR, 1H NMR, 13C NMR, and mass spectral data, while their abilities to inhibit growth of Mycobacterium tuberculosis in vitro have been determined. The results show that compounds 5a, 5c, 5d, 5g, and 5k exhibited excellent antitubercular activity with percentage inhibition of 96, 90, 94, 93, and 92, respectively at a minimum inhibitory concentration (MIC) of <6.25 μg/mL, whereas compounds 5b, 5e, 5f, 5h, 5i, 5j, and 5l exhibited moderate- to- good antitubercular activity with percentage inhibition of 68, 70, 67, 64, 59, 73, and 67, respectively, at a MIC of >6.25 μg/mL. From the secondary screening, the actual MIC of compounds 5a, 5c, 5d, 5g, and 5k are <3.125.
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References
Aggarwal R, Singh SP, Kumar V, Tyagi P (2006) Synthesis and antibacterial activity of some new 1-heteroaryl-5-amino-3H/methyl-4-phenylpyrazoles. Bioorg Med Chem 14:1785–1791. doi:10.1016/j.bmc.2005.10.026
Alafeefy AM (2008) Synthesis and antimicrobial activity of some new quinazolin-4(3H)-one derivatives. Pharm Biol 46(10):751–756
Apfel C, Banner DW, Bur D, Dietz M, Hubschwerlen C, Locher H, Marlin F, Masciadri R, Pirson W, Stalder H (2001) 2-(2-Oxo-1,4-dihydro-2H-quinazoli-3-yl)- and 2-(2,2-dioxo-1,4-dihydro-2H-6 benzo[1,2,6]thiadiazin-3-yl)-N-hydroxy-acetamides as potent and selective peptide deformylase inhibitors. J Med Chem 44:1847–1852
Chenard BL, Welch WM, Blake JF, Butler TW, Reinhold A, Ewing FE, Menniti FS, Pagnozzi MJ (2001) Quinazolin-4-one a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists: structure–activity relationship of the C-2 side chain tether. J Med Chem 44:1710–1717
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
Deohate PP, Deohate JP, Berad BN (2004) Synthesis of some novel 1,2,4-dithiazolidines and their antibacterial and antifungal activity. Asian J Chem 16:255–260
Guang-Fang X, Bao-An S, Pinaki SB, Song Y, Pei-Quan Z, Lin-Hong J, Wei X, De-Yu H, Ping L (2007) Synthesis and antifungal activity of novel S-substituted 6-fluoro-4-alkyl(aryl)thioquinazoline derivatives. Bioorg Med Chem 15:3768–3774
Habeeb AG, Rao PNP, Knaus EE (2001) Design and synthesis of celecoxib and rofecoxib analogues as selective cyclooxygenase-2 (COX-2) inhibitors: replacement of sulfonamide and methylsulfonyl pharmacophores by an azido bioisostere. J Med Chem 44:3039–3042. doi:10.1021/jm010153c
Kees KL, Fitzgerald JJ, Steiner KE, Mattes JF, Mihan B, Tosi T, Moondoro D, McCaleb ML (1996) New potent antihyperglycemic in db/db mice: synthesis and structure-activity relationship studies of (4-substituted benzyl)(trifloromethyl)pyrazoles and -pyrazolones. J Med Chem 39:3920–3928. doi:10.1021/jm960444z
Martel AM, Graul A, Rabbaseda X, Castaner R (1997) Slidenafil: treatment of erectile dysfunction, phosphodiesterase V inhibitor. Drugs Future 22:138–143
Meazza G, Bettarini F, Porta PL, Piccardi P, Signorini E, Portoso D, Fornara L (2004) Synthesis and herbicidal activity of novel heterocyclic protoporphyrinogen oxidase inhibitors. Pest Manag Sci 60:1178–1188. doi:10.1002/ps.923
Park H-J, Lee K, Park S-J, Ahn B, Lee J-C, Cho HY, Lee K-I (2005) Identification of antitumor activity of pyrazole oxime ethers. Bioorg Med Chem Lett 15:3307–3312. doi:10.1016/j.bmcl.2005.03.082
Raffa D, Daidone G, Schillaci D, Maggio B, Plescia F (1999) Synthesis of new 3-(3-phenyl-isoxazo-5-yl) or 3-[(3-phenylisoxazol-5-yl)-amino]-substituted 4(3H)quinazolinone derivatives with antineoplastic activity. Pharmazie 54:251–254
Rattan A, Kalia A, Ahmad N (1998) Multidrug-resistant Mycobacterium tuberculosis: molecular perspectives. Emerg Infect Dis 4:195–199
Siddappa K, Reddy T, Reddy CV (2008) Synthesis, characterization and antimicrobial studies of 3-[(2-hydroxy-quinolin-3-ylmethylene)-amino]-2-phenyl-3H-quinazolin-4-one and its metal(II) complexes. E J Chem 5:155–162
Singh P, Mishra AK, Malonia SK, Chauhan DS, Sharma VD, Venkatesan K, Katoch VM (2006) The paradox of pyrazinamide: an update on the molecular mechanisms of pyrazinamide resistance in Mycobacteria. J Commun Dis 38(3):288–298
Suling WJ, Seitz LE, Pathak V, Barrow WW, Reynolds RC (2000) Antimycobacterial activities of 2,4-diamino-5-deazapteridine derivatives and effects on mycobacterial dihydrofolate reductase. Antimicrob Agents Chemother 44(10):2784–2793
Tobe M, Isobe Y, Tomizawa H, Nagasaki T, Obara F, Hayashi H (2003) Structure–activity relationships of 6-fluoroquinazolines: dual-acting compounds with inhibitory activities toward both TNF alpha production and T cell proliferation. Bioorg Med Chem 11:609–616
Wustrow DJ, Rubin CR, Knobelsdorf JA, Akunne H, MacKenzie DR, Pugsley TA, Zoski KT, Heffner TG, Wise LD (1998) Pyrazolo[1,5-a]pyrimidine CRF-1 receptor antagonists. Bioorg Med Chem Lett 8:2067–2070. doi:10.1016/S0960-894X(98)00372-2
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The authors are thankful to Cadila Pharmaceuticals Limited, Dholka, Ahmedabad for providing research and library facilities.
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Pandit, U., Dodiya, A. Synthesis and antitubercular activity of novel pyrazole–quinazolinone hybrid analogs. Med Chem Res 22, 3364–3371 (2013). https://doi.org/10.1007/s00044-012-0351-0
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DOI: https://doi.org/10.1007/s00044-012-0351-0