Synthesis, biological evaluation and structure-activity relationship of 2-styrylquinazolones as anti-tubercular agents

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• 作者：Pradeep S. Jadhavar^a ; Tejas M. Dhameliya^a ; Maulikkumar D. Vaja^a ; Dinesh Kumar^a ; Jonnalagadda Padma Sridevi^b ; Perumal Yogeeswari^b ; Dharmarajan Sriram^b ; Asit K. Chakraborti^a ; ^{akchakraborti@niper.ac.in" class="auth_mail" title="E-mail the corresponding author} ; ^{akchakraborti@rediffmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Tuberculosis ; 2-Styrylquinazolone ; Anti-TB agents ; H37Rv strain ; SAR
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：1 June 2016
• 年：2016
• 卷：26
• 期：11
• 页码：2663-2669
• 全文大小：2764 K

文摘

2-Styrylquinazolones are reported as a novel class of potent anti-mycobacterial agents. Forty-six target compounds have been synthesized using one pot reaction involving isatoic anhydride, amine, and triethyl orthoacetate followed by aldehyde to construct the 2-styrylquinazolone scaffold. The anti-mycobacterial potency of the compounds was determined against H₃₇Rv strain. Twenty-six compounds exhibited anti-Mtb activity in the range of 0.40–6.25 μg/mL. Three compounds 8c, 8d and 8ab showed MIC of 0.78 μg/mL and were found to be non-toxic (<50% inhibition at 50 μg/mL) to HEK 293T cell lines with the therapeutic index >64. The most potent compound 8ar showed MIC of 0.40 μg/mL with the therapeutic index >125. An early structure activity relationship for this class of compounds has been established. The computational studies indicate the possibility of these compounds binding to the penicillin binding proteins (PBPs).