Design, synthesis and biological evaluation of novel hybrids of N-aryl pyrrothine-base α-pyrone as bacterial RNA polymerase inhibitors. Issue 11 (1st June 2020)

• Record Type: Journal Article
• Authors: Tan, Xiangduan; Huang, Mohan; Nian, Siyun; Peng, Yanfen; Qin, Jianli; Kong, Bo; Duan, Xiaoqun
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 30:Issue 11(2020)
• Publication Date: 2020-06-01
• Subjects: Bacterial RNA polymerase -- Switch region -- N-aryl pyrrothine -- α-pyrone -- Hybrid; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2020.127146
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Antibiotic resistance in bacteria has been an emerging public health problem, thus discovery of novel and effective antibiotics is urgent. A series of novel hybrids of N -aryl pyrrothine-base α -pyrone hybrids was designed, synthesized and evaluated as bacterial RNA polymerase (RNAP) inhibitors. Among them, compound 13c exhibited potent antibacterial activity against antibiotic-resistant S. aureus with the minimum inhibitory concentration (MIC) in the range of 1–4 μg/mL. Moreover, compound 13c exhibited strong inhibitory activity against E.coli RNAP with IC50 value of 16.06 μM, and cytotoxicity in HepG2 cells with IC50 value of 7.04 μM. The molecular docking study further suggested that compound 13c binds to the switch region of bacterial RNAP. In summary, compound 13c is a novel bacterial RNAP inhibitor, and a promising lead compound for further optimization.