title: Design, Synthesis, and Antimicrobial Evaluation of Novel Quinolone Imidazoles and Interactions with MRSA DNA.
abstract: A novel series of quinolone imidazoles as new type of antimicrobial agents were synthesized. Most compounds exhibited good bioactivities especially against MRSA even superior to reference drugs. They induced bacterial resistance more slowly than clinical drugs and gave low cytotoxicity to human cells. The pKa values of these compounds showed appropriate ranges to pharmacokinetic behaviors. The interactions between compound 8b, Cu(2+) ion, and MRSA DNA revealed that compound 8b could intercalate into DNA through copper ion bridge to form a steady 8b-Cu(2+) -DNA ternary complex which might further block DNA replication to exert the powerful bioactivities. Study of compound 8b with human serum albumin indicated that compound 8b could be effectively stored and carried by human serum albumin.
authors: 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: Ling
authors: L
authors: Zhang
authors: 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: Kannekanti Vijaya
authors: KV
authors: Kumar
authors: 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: Syed
authors: S
authors: Rasheed
authors: 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: Rong-Xia
authors: RX
authors: Geng
authors: 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: Cheng-He
authors: CH
authors: Zhou
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D003300:Copper / Q000737:chemistry / Q000378:metabolism; D004269:DNA, Bacterial / Q000187:drug effects / Q000378:metabolism; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics; D008826:Microbial Sensitivity Tests; D015363:Quinolones / Q000737:chemistry / Q000494:pharmacology; D012709:Serum Albumin / Q000737:chemistry
chemical_list: D000890:Anti-Infective Agents; D004269:DNA, Bacterial; D007093:Imidazoles; D015363:Quinolones; D012709:Serum Albumin; D003300:Copper
keywords: DNA; anti-MRSA; human serum albumin; imidazole; quinolone