Design, synthesis and biological evaluation of 5-fluorouracil-derived benzimidazoles as novel type of potential antimicrobial agents.
A series of 5-fluorouracil benzimidazoles as novel type of potential antimicrobial agents were designed and synthesized for the first time. Bioactive assay manifested that some of the prepared compounds exhibited good or even stronger antibacterial and antifungal activities against the tested strains in comparison with reference drugs norfloxacin, chloromycin and fluconazole. Noticeably, 3-fluorobenzyl benzimidazole derivative 5c gave remarkable antimicrobial activities against Saccharomyces cerevisiae, MRSA and Bacillus proteus with MIC values of 1, 2 and 4μg/mL, respectively. Experimental research revealed that compound 5c could effectively intercalate into calf thymus DNA to form compound 5c-DNA complex which might block DNA replication and thus exert antimicrobial activities. Molecular docking indicated that compound 5c should bind with DNA topoisomerase IA through three hydrogen bonds by the use of fluorine atom and oxygen atoms in 5-fluorouracil with the residue Lys 423.
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, PR China.
Xue-Jie
XJ
Fang
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, PR China.
Ponmani
P
Jeyakkumar
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, PR China.
Srinivasa Rao
SR
Avula
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, PR China.
Qian
Q
Zhou
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, PR China. Electronic address: zhouch@swu.edu.cn.
Cheng-He
CH
Zhou
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005472:Fluorouracil / Q000737:chemistry / Q000494:pharmacology*; D005658:Fungi / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D001562:Benzimidazoles; D005472:Fluorouracil
5-Fluorouracil; Antibacterial; Antifungal; Benzimidazole; DNA