Ozadali Keriman, Tan Oya Unsal, Yogeeswari Perumal, Dharmarajan Sriram, Balkan Ayla
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey.
Bioorg Med Chem Lett. 2014 Apr 1;24(7):1695-7. doi: 10.1016/j.bmcl.2014.02.052. Epub 2014 Mar 1.
This Letter reports the synthesis and evaluation of some thiazolylhydrazone derivatives for their in vitro antimycobacterial activities against Mycobacterium tuberculosis H37Rv. The cytotoxic activities of all compounds were also evaluated. The compounds exhibited promising antimycobacterial activity with MICs of 1.03-72.46 μM and weak cytotoxicity (8.9-36.8% at 50 μg/mL). Among them, 1-(4-(1H-1,2,4-triazol-1-yl)benzylidene)-2-(4-(4-nitrophenyl)thiazol-2-yl)hydrazine 10 was found to be the most active compound (MIC of 1.03 μM) with a good safety profile (16.4% at 50 μg/mL). Molecular modeling studies were done to have an idea for the mechanism of the action of the target compounds. According the docking results it can be claimed that these compounds may bind most likely to TMPK than InhA or CYP121.
本信函报道了一些噻唑基腙衍生物的合成及其对结核分枝杆菌H37Rv的体外抗分枝杆菌活性评估。还评估了所有化合物的细胞毒性活性。这些化合物表现出有前景的抗分枝杆菌活性，最低抑菌浓度（MIC）为1.03 - 72.46 μM，且细胞毒性较弱（50 μg/mL时为8.9 - 36.8%）。其中，1-(4-(1H - 1,2,4 - 三唑 - 1 - 基)亚苄基)-2-(4-(4 - 硝基苯基)噻唑 - 2 - 基)肼10被发现是活性最高的化合物（MIC为1.03 μM），具有良好的安全性（50 μg/mL时为16.4%）。进行了分子模拟研究以了解目标化合物的作用机制。根据对接结果，可以声称这些化合物与胸苷酸磷酸化酶（TMPK）结合的可能性比与烯酰基载体蛋白还原酶（InhA）或细胞色素P450 121（CYP121）结合的可能性更大。
