Trisubstituted Aryl Cyclohexanecarboxylates (TACC): A Simple, New Molecular Scaffold for Antibiotics Design

• 作者: Arianna Kazez Daniel W. Carney Jason K. Sello Olusegun B. Olubanwo
• 来源期刊: 有机化学国际期刊(英文)
• 学科: 化学
• 关键词: Cyclohexanecarboxylate Oxocyclohexanecarboxylate CLPP Activator Bacillus SUBTILIS Antibacterial ANTIBIOTICS Pseudo-Robinson Protocol PHARMACOPHORES CLP Protease
• 年，卷（期）: 2019,（3）
• 页码范围: 142-162
• 页数: 21页
• 分类号: O6

摘要

A new class of potential antibacterial agents has been synthesized on a new molecular scaffold of cyclohexane carboxylate. We have tagged this new class of compounds TACCs (Trisubstituted Aryl Cyclohexanecarboxylate). These new molecules are structural analogues of an Activators of Self-Compartmentalizing Proteases 4 and 5 (ACP 4 and 5), and were synthesized to circumvent the drug-like property (drug-ability) challenges and liability noted in ACP 4 and 5. A pseudo-Robinson annulation protocol was used to furnish this new class of potential antibiotics. Structure-activity relationship (SAR) study was done to identify the pharmacophore(s) in this molecular scaffold. A selection of these compounds was used in our preliminary antibacterial inhibitory activities’ studies on Bacillus mycoides and Bacillus subtilis. These preliminary studies show that the TACCs exhibited equal, and in some cases better, antibacterial activity than ACP 4 and 5.