Email this article Docking study, synthesis and antimicrobial evaluation of some novel 4-anilinoquinazoline derivatives
Abstract
A series of novel 4-anilinoquinazoline derivatives were designed and synthesized from benzoic acid through ring closure, chlorination or nucleophilic substitution. The structures of compounds were characterized by IR, 1H-NMR and mass spectroscopy. All synthesized derivatives were screened for their antimicrobial activities against Gram-positive (Staphylococcus aurous, Bacillus subtilis, Listeria monocitogenes) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa, Salmonella entritidis) bacteria and also for antifungal activities against Candida albicans using the conventional micro dilution method. Most of the compounds have shown good antibacterial activities, especially compound 4c having highest activities against E. coli at 32 μg/mL concentration while the tested compounds did not exhibited remarkable antifungal activities. The potential DNA gyrase inhibitory activity of these compounds was investigated in silico using molecular docking simulation method. All compounds showed good results especially compound 4c which showed the lowest ∆Gbind results (-8.16 Kcal/mol).
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Gupta B, Singh S. Antibiotics- new tools in current and future drug therapy. Journal Of Scientific & Innovative Research. 2012;1(1):27-42.
Collin F, Karkare S, Maxwell A. Exploiting bacterial DNA gyrase as a drug target: current state and perspectives. Appl Microbiol Biotechnol. 2011;92(3):479-497.
Ostrov DA, Prada JAH, Corsino PE, Finton KA, Le N, Rowe TC. Discovery of novel DNA gyrase inhibitors by high-throughput virtual screening. Antimicrob Agents Chemother. 2007;51(10):3688-3698.
Heddle J, Maxwell A. Quinolone-binding pocket of DNA gyrase: role of GyrB. Antimicrob Agents Chemother. 2002;46(6):1805-1815.
Kumar R, Madhumathi BS, Nagaraja V. Molecular basis for the differential quinolone susceptibility of mycobacterial DNA gyrase. Antimicrob Agents Chemother. 2014;58(4):2013-2020.
Kumar A, Sharma P, Kumari P, Kalal BL. Exploration of antimicrobial and antioxidant potential of newly synthesized 2, 3-disubstituted quinazoline-4 (3H)-ones. Bioorg Med Chem Lett. 2011;21(14):4353-4357.
Khodarahmi G, Jafari E, Hakimelahi G, Abedi D, Khajouei MR, Hassanzadeh F. Synthesis of some new quinazolinone derivatives and evaluation of their antimicrobial activities. Iran J Pharm Res. 2012;11(3):789-797.
Laddha SS, Wadodkar SG, Meghal SK. Studies on some biologically active substituted 4(3H)-quinazolinones. Part 1. Synthesis, characterization and anti-inflammatory#-antimicrobial activity$ of 6,8-disubstituted 2-phenyl-3-[substituted-benzothiazol-2-yl]-4(3H)-quinazolinones. ARKIVOC. 2006;Xi:1-20.
Abouzid K, Shouman S. Design, synthesis and in vitro antitumor activity of 4-aminoquinoline and 4-aminoquinazoline derivatives targeting EGFR tyrosine kinase. Bioorg. Med Chem. 2008;16(16):7543-7551.
Jafari E, Khodarahmi G, Hakimelahi G, Tsai F, Hassanzadeh F. Synthesis of some new tricyclic 4 (3H)-quinazolinone derivatives. Res Pharm Sci. 2011;6(2):93-100.
Rezaee Nasab R, Karami B, Khodabakhshi S. Selective solvent-free biginelli condensation using Tungestat Sulfuric Acid as powerful and reusable catalyst. Bulletin of chemical reaction engineering& catalysis. 2014;9(2):148-154.
Gilbert IH. Inhibitors of dihydrofolate reductase in Leishmania and trypanosomes. Biochim Biophys Acta.. 2002;1587(2):249-257.
Jackman AL, Taylor GA, Gibson W, Kimbell R, Brown M, Calvert AH, et al. ICI D1694, a quinazoline antifolate thymidylate synthase inhibitor that is a potent inhibitor of L1210 tumor cell growth in vitro and in vivo: a new agent for clinical study. Cancer Res. 1991;51(20):5579-5586.
Ismail RS, Ismail NS, Abuserii S, El Ella DAA. Recent advances in 4-aminoquinazoline based scaffold derivatives targeting EGFR kinases as anticancer agents. Future Journal of Pharmaceutical Sciences. 2016;2(1):9-19.
de Castro Barbosa ML, Lima LM, Tesch R, Sant'Anna CMR, Totzke F, Kubbutat MH, et al. Novel 2-chloro-4-anilino-quinazoline derivatives as EGFR and VEGFR-2 dual inhibitors. Eur J Med Chem. 2014;71:1-14.
Thomsen R, Christensen MH. MolDock: a new technique for high-accuracy molecular docking. J Med Chem. 2006;49(11):3315-3321.
Jiang N, Zhai X, Zhao Y, Liu Y, Qi B, Tao H, et al. Synthesis and biological evaluation of novel 2-(2-arylmethylene) hydrazinyl-4-aminoquinazoline derivatives as potent antitumor agents. Eur J Med Chem. 2012;54:534-541.
Pawar VG, Sos ML, Rode HB, Rabiller M, Heynck S, Van Otterlo WA, et al. Synthesis and biological evaluation of 4-anilinoquinolines as potent inhibitors of epidermal growth factor receptor. J Med Chem 2010;53(7):2892-2901.
Bansal S, Kumar S, Aggarwal V, Joseph A. Design, synthesis, docking study & antibacterial evaluation of 1, 3-diarylpyrazolyl substituted indolin-2-ones. Indo Global Journal of Pharmaceutical Sciences. 2014;4(1):1-7.
Jayashree B, Thomas S, Nayak Y. Design and synthesis of 2-quinolones as antioxidants and antimicrobials: a rational approach. Med Chem Res. 2010;19(2):193-209.
Mansourian M, Fassihi A, Saghaie L, Madadkar-Sobhani A, Mahnam K, Abbasi M. QSAR and docking analysis of A2B adenosine receptor antagonists based on non-xanthine scaffold. Med Chem Res. 2015;24:394-407.
Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, et al. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem. 1998;19(14):1639-1662.
Jayalakshmi B, Raveesha K, Amruthesh K. Evaluation of antibacterial and antioxidant potential of Euphorbia cotinifolia linn. leaf extracts. Chem Ind Chem Eng Q. 2014;20(1):19-28.
Wiegand I, Hilpert K, Hancock RE. Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nature Protocols. 2008;3(2):163-715.
Baker CN, Banerjee SN, Tenover FC. Evaluation of Alamar colorimetric MIC method for antimicrobial susceptibility testing of Gram-negative bacteria. J Clin Microbiol. 1994;32(5):1261-1267.
Kampranis SC, Gormley NA, Tranter R, Orphanides G, Maxwell A. Probing the binding of coumarins and cyclothialidines to DNA gyrase. Biochemistry. 1999;38:1967–1976.
Lewis RJ, Singh OMP, Smith CV, Skarzynski T, Maxwell A, Wonacott AJ, et al. The nature of inhibition of DNA gyrase by the coumarins and the cyclothialidines revealed by X-ray crystallography. EMBO J. 1996;15:1412–1420.
Blance SJ, Williams NL, Preston ZA, Bishara J, Smyth MS, Maxwell A. Temperature-sensitive suppressor mutations of the Escherichia coli DNA gyrase B protein. Protein Sci. 2000;9(5):1035-1037.
Boyapati S, Kulandaivelu U, Sangu S, Vanga MR. Synthesis, antimicrobial evaluation, and docking studies of novel 4‐substituted quinazoline derivatives as DNA‐gyrase inhibitors. Archiv der Pharmazie. 2010;343(10):570-576.
Mladenović M, Vuković N, Sukdolak S, Solujić S. Design of novel 4-hydroxy-chromene-2-one derivatives as antimicrobial agents. Molecules. 2010;15(6):4294-4308.
Perumal P, Pandey VP, Parasuraman P. Docking studies on some novel piperidine analogues against DNA gyrase enzyme. Inventi Rapid Molecular Modeling. 2014;1:1-4.
Patil RB, Sawant SD. Synthesis, characterization, molecular docking and evaluation of antimicrobial activity of some 3-heteroaryl substituted chromen-2-one derivatives. Int J Pharm Tech Res. 2014-2015;7(3):471-480.
Salih NA. Synthesis of some new quinazolin-4 (3h)-one derivatives and study of their some antibacterial studies of novel 4‐substituted quinazoline derivatives as DNA‐gyrase inhibitors. Archiv der Pharmazie. 2010;343(10):570-576.
Mladenović M, Vuković N, Sukdolak S, Solujić S. Design of novel 4-hydroxy-chromene-2-one derivatives as antimicrobial agents. Molecules. 2010;15(6):4294-4308.
Perumal P, Pandey VP, Parasuraman P. Docking studies on some novel piperidine analogues against DNA gyrase enzyme. Inventi Rapid Molecular Modeling. 2014;1:1-4.
Patil RB, Sawant SD. Synthesis, characterization, molecular docking and evaluation of antimicrobial activity of some 3-heteroaryl substituted chromen-2-one derivatives. Int J Pharm Tech Res. 2014-2015;7(3):471-480.
Salih NA. Synthesis of some new quinazolin-4 (3h)-one derivatives and study of their some antibacterial activity. Journal of Al-Nahrain University. 2008;11(2):16-23.
Li F, Feng Y, Meng Q, Li W, Li Z, Wang Q, et al. An efficient construction of quinazolin-4 (3H)-ones under microwave irradiation. Arkivoc. 2007;1: 40-50.
Arnott EA, Chan LC, Cox BG, Meyrick B, Phillips A. POCl3 chlorination of 4-quinazolones. J Org Chem. 2011;76(6):1653-1661.
El-Azab AS, Al-Omar MA, Alaa A-M, Abdel-Aziz NI, Magda A-A, Aleisa AM, et al. Design, synthesis and biological evaluation of novel quinazoline derivatives as potential antitumor agents: molecular docking study. Eur J Med Chem. 2010;45(9): 4188-4198.
Van Horn KS, Burda WN, Fleeman R, Shaw LN, Manetsch R. Antibacterial activity of a series of N 2, N 4-disubstituted quinazoline-2, 4-diamines. J Med Chem. 2014;57(7):3075-3093.
Gottasová R, Kubíková J. Antibacterial effect of some 2, 6-disubstituted 4-anilinoquinazolines. Folia Microbiologica. 1998;43(6):679-682.
Parhi AK, Zhang Y, Saionz KW, Pradhan P, Kaul M, Trivedi K, et al. Antibacterial activity of quinoxalines, quinazolines, and 1, 5-naphthyridines. Bioorg Med Chem Lett. 2013;23(17):4968-4974.
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