Identification of novel 2-aminothiazole conjugated nitrofuran as antitubercular and antibacterial agents.
The emergence of antibiotic resistant pathogens is an ongoing main problem in the therapy of bacterial infections. In order to develop promising antitubercular and antibacterial lead compounds, we designed and synthesized a new series of derivatives of 2-aminothiazole conjugated nitrofuran with activities against both Mycobacterium tuberculosis and Staphylococcus aureus. Eight compounds 12e, 12k, 12l, 12m, 18a, 18d, 18e, and 18j emerged as promising antitubercular agents. Structure-activity relationships (SARs) were discussed and showed that the derivatives substituted at the position-3 of benzene of 5-nitro-N-(4-phenylthiazol-2-yl)furan-2-carboxamide exhibited superior potency. The most potent compound 18e, substituted with benzamide at this position, displayed minimum inhibitory concentrations (MICs) of 0.27μg/mL against Mtb H37Ra and 1.36μg/mL against S. aureus. Furthermore, compound 18e had no obvious cytotoxicity to normal Vero cells (IC50=50.2μM). The results suggest that the novel scaffolds of aminothiazole conjugated nitrofuran would be a promising class of potent antitubercular and antimicrobial agents.
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
Kai
K
Ran
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
Chao
C
Gao
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
Hongxia
H
Deng
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
Qian
Q
Lei
Department of Pharmaceutical and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu, Sichuan 610065, China.
Xinyu
X
You
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
Ningyu
N
Wang
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
Yaojie
Y
Shi
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
Zhihao
Z
Liu
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
Wei
W
Wei
Department of Pharmaceutical and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu, Sichuan 610065, China.
Cuiting
C
Peng
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
Lu
L
Xiong
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
Kunjie
K
Xiao
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China; Department of Pharmaceutical and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu, Sichuan 610065, China. Electronic address: yuluot@scu.edu.cn.
Luoting
L
Yu
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D009581:Nitrofurans / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology; D014709:Vero Cells
D000900:Anti-Bacterial Agents; D009581:Nitrofurans; D013844:Thiazoles; C004483:2-aminothiazole
Aminothiazole; Mycobacterium tuberculosis; Nitrofuran; Staphylococcus aureus; Structure–activity relationships (SARs)