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ID: ALA4480441

Journal: Bioorg Med Chem

Title: Discovery and development of novel rhodanine derivatives targeting enoyl-acyl carrier protein reductase.

Authors: Xu JF, Wang TT, Yuan Q, Duan YT, Xu YJ, Lv PC, Wang XM, Yang YS, Zhu HL.

Abstract: A series of rhodanine derivatives RB1-RB23 were synthesized through a two-round screening. Their Mycobacterial tuberculosis (Mtb) InhA inhibitory activity and Mtb growth blocking capability were evaluated. The most potent hit compound RB23 indicated comparable InhA inhibiton (IC50 = 2.55 μM) with the positive control Triclosan (IC50 = 6.14 μM) and Isoniazid (IC50 = 8.29 μM). Its improved growth-blocking effect on Mtb and low toxicity were attractive for further development. The docking simulation revealed the possible binding pattern of this series and picked the key interacted residues as Ser20, Phe149, Lys165 and Thr196. The 3D-QSAR model visualized the SAR discussion and hinted new information. Modifying the surroundings near rhodanine moiety might be promising attempts in later investigations.

CiteXplore: 30846404

DOI: 10.1016/j.bmc.2019.02.043