Biphenyl tetrazole-thiazolidinediones as novel bacterial peptide deformylase inhibitors: Synthesis, biological evaluations and molecular docking study

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• 作者：Firoz A.Kalam Khan^a ; Kaivalya S. Jadhav^a ; Rajendra H. Patil^b ; Devanand B. Shinde^c ; Rohidas B. Arote^d ; ^{rohi06@snu.ac.k" class="auth_mail" title="E-mail the corresponding author} ; Jaiprakash N. Sangshetti^a ; ^{jnsangshetti@rediffmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Biphenyl tetrazole-thiazolidinediones ; PDF inhibition ; Antibacterial activity ; Molecular docking study
• 刊名：Biomedicine & Pharmacotherapy
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：83
• 期：Complete
• 页码：1146-1153
• 全文大小：1266 K

文摘

Herein, we report the synthesis and screening of biphenyl tetrazole-thiazolidinediones 14(a-j) as bacterial Peptide deformylase (PDF) enzyme inhibitors. The compounds 14b (IC₅₀ value = 16.25 μM), 14c (IC₅₀ value = 18.00 μM) and 14h (IC₅₀ value = 17.25 μM) had shown good PDF inhibition activity. The compounds 14b (MIC range = 20.75–35.41 μg/mL), 14c (MIC range = 19.41–26.00 μg/mL) and 14d (MIC range = 8.41–8.58 μg/mL) had also shown potent antibacterial activity when compared with standard ciprofloxacin (MIC range = 25–50 μg/mL). Thus, the active derivatives were not only potent PDF inhibitors but also efficient antibacterial agents. In order to gain more insight on the binding mode of the compounds with PDF enzyme, the synthesized compounds 14(a-j) were docked against PDF enzyme of E. coli and compounds exhibited good binding properties. The results suggest that this class of compounds have been potential for development and use in a future as antibacterial drugs.