title: Multi-targeting exploration of new 2-aminothiazolyl quinolones: Synthesis, antimicrobial evaluation, interaction with DNA, combination with topoisomerase IV and penetrability into cells.
abstract: A series of new potentially multi-targeting antimicrobial 2-aminothiazolyl quinolones were designed, synthesized and characterized by1H NMR,13C NMR, IR, MS and HRMS spectra. Bioactive assay manifested that some of the prepared compounds showed moderate to good antibacterial and antifungal activities. Noticeably, compound 10f could effectively inhibit the growth of B. typhi and MRSA with MIC values of 1 and 8 μg/mL, respectively. Experimental results revealed that compound 10f was membrane-active and had the ability to rapidly kill the tested strains and effectively prevent the development of bacterial resistance. Moreover, this compound also exhibited low toxicity against L929 cells. Molecular docking indicated that compound 10f could bind with topoisomerase IV-DNA complexes through hydrogen bonds and hydrophobic interactions. Quantum chemical studies were also performed on 10f to understand the structural features essential for activity. The preliminary mechanism research suggested that compound 10f could intercalate into calf thymus DNA to form a steady supramolecular complex which might block DNA replication to exert the powerful bioactivities.
authors: Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
authors: Yu
authors: Y
authors: Cheng
authors: Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
authors: Srinivasa Rao
authors: SR
authors: Avula
authors: Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
authors: Wei-Wei
authors: WW
authors: Gao
authors: Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
authors: Dinesh
authors: D
authors: Addla
authors: Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
authors: Vijai Kumar Reddy
authors: VKR
authors: Tangadanchu
authors: Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
authors: Ling
authors: L
authors: Zhang
authors: Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu 610072, China. Electronic address: feiyu127@126.com.
authors: Jian-Mei
authors: JM
authors: Lin
authors: Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China. Electronic address: zhouch@swu.edu.cn.
authors: Cheng-He
authors: CH
authors: Zhou
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology* / Q000633:toxicity; D001692:Biological Transport; D002417:Cattle; D002460:Cell Line; D002463:Cell Membrane Permeability; D060326:Chemistry Techniques, Synthetic; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication / Q000187:drug effects; D027101:DNA Topoisomerase IV / Q000737:chemistry / Q000378:metabolism*; D015195:Drug Design; D007700:Kinetics; D051379:Mice; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D010539:Permeability; D015363:Quinolones / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000890:Anti-Infective Agents; D015363:Quinolones; D004247:DNA; C427203:calf thymus DNA; D027101:DNA Topoisomerase IV
keywords: Aminothiazole; Antibacterial; Antifungal; Molecular modeling; Quantum chemical studies; Quinolone