TITLE:
Trisubstituted Aryl Cyclohexanecarboxylates (TACC): A Simple, New Molecular Scaffold for Antibiotics Design
AUTHORS:
Olusegun B. Olubanwo, Arianna Kazez, Daniel W. Carney, Jason K. Sello
KEYWORDS:
Cyclohexanecarboxylate, Oxocyclohexanecarboxylate, ClpP Activator, Bacillus Subtilis, Antibacterial, Antibiotics, Pseudo-Robinson Protocol, Pharmacophores, Clp Protease
JOURNAL NAME:
International Journal of Organic Chemistry,
Vol.9 No.3,
September
18,
2019
ABSTRACT: 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.