title: Discovery of membrane active benzimidazole quinolones-based topoisomerase inhibitors as potential DNA-binding antimicrobial agents.
abstract: A series of novel benzimidazole quinolones as potential antimicrobial agents were designed and synthesized. Most of the prepared compounds exhibited good or even stronger antimicrobial activities in comparison with reference drugs. The most potent compound 15m was membrane active and did not trigger the development of resistance in bacteria. It not only inhibited the formation of biofilms but also disrupted the established Staphylococcus aureus and Escherichia coli biofilms. It was able to inhibit the relaxation activity of E. coli topoisomerase IV at 10 μM concentration. Moreover, this compound also showed low toxicity against mammalian cells. Molecular modeling and experimental investigation of compound 15m with DNA suggested that this compound could effectively bind with DNA to form a steady 15m-DNA complex which might further block DNA replication to exert the powerful bioactivities.
authors.affiliation: Key Laboratory of Applied Chemistry of Chongqing Municipality, Institute of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Applied Chemistry of Chongqing Municipality, Institute of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Addla
authors.affiliation: Key Laboratory of Applied Chemistry of Chongqing Municipality, Institute of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
authors.forename: Jeyakkumar
authors.initials: J
authors.lastname: Ponmani
authors.affiliation: Key Laboratory of Applied Chemistry of Chongqing Municipality, Institute of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
authors.forename: Ao
authors.initials: A
authors.lastname: Wang
authors.affiliation: Key Laboratory of Applied Chemistry of Chongqing Municipality, Institute of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
authors.affiliation: Key Laboratory of Applied Chemistry of Chongqing Municipality, Institute of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Wang
authors.affiliation: Key Laboratory of Applied Chemistry of Chongqing Municipality, Institute of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
authors.forename: Shao-Lin
authors.initials: SL
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Applied Chemistry of Chongqing Municipality, Institute of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
authors.forename: Rong-Xia
authors.initials: RX
authors.lastname: Geng
authors.affiliation: Key Laboratory of Applied Chemistry of Chongqing Municipality, Institute of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
authors.forename: Gui-Xin
authors.initials: GX
authors.lastname: Cai
authors.affiliation: School of Chemical Engineering, Chongqing University of Technology, Chongqing 400054, China. Electronic address: lishuo@cqut.edu.cn.
authors.forename: Shuo
authors.initials: S
authors.lastname: Li
authors.affiliation: Key Laboratory of Applied Chemistry of Chongqing Municipality, Institute of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China. Electronic address: zhouch@swu.edu.cn.
authors.forename: Cheng-He
authors.initials: CH
authors.lastname: Zhou
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001562:Benzimidazoles / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D004269:DNA, Bacterial / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D015363:Quinolones / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D059003:Topoisomerase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001562:Benzimidazoles; D004269:DNA, Bacterial; D015363:Quinolones; D059003:Topoisomerase Inhibitors
keywords: Anti-MRSA; Benzimidazole; DNA; Quinolone; Topoisomerase