Yadav Snehlata, Lim Siong Meng, Ramasamy Kalavathy, Vasudevan Mani, Shah Syed Adnan Ali, Mathur Abhishek, Narasimhan Balasubramanian
Faculty of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, 124001, India.
Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), 42300, Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.
Chem Cent J. 2018 May 26;12(1):66. doi: 10.1186/s13065-018-0432-3.
The study describes the synthesis, characterization, in vitro antimicrobial and anticancer evaluation of a series of 2-(1-benzoyl-1H-benzo[d]imidazol-2-ylthio)-N-substituted acetamide derivatives. The synthesized derivatives were also assessed for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. The compounds found active in in vitro study were assessed for their in vivo antitubercular activity in mice models and for their inhibitory action on vital mycobacterial enzymes viz, isocitrate lyase, pantothenate synthetase and chorismate mutase.
Compounds 8, 9 and 11 emerged out as excellent antimicrobial agents in antimicrobial assays when compared to standard antibacterial and antifungal drugs. The results of anticancer activity displayed that majority of the derivatives were less cytotoxic than standard drugs (tamoxifen and 5-fluorouracil) towards MCF7 and HCT116 cell lines. However, compound 2 (IC = 0.0047 µM/ml) and compound 10 (IC = 0.0058 µM/ml) showed highest cytotoxicity against MCF7 and HCT116 cell lines, respectively. The results of in vivo antitubercular activity revealed that a dose of 1.34 mg/kg was found to be safe for the synthesized compounds. The toxic dose of the compounds was 5.67 mg/kg while lethal dose varied from 1.81 to 3.17 mg/kg body weight of the mice. Compound 18 inhibited all the three mycobacterial enzymes to the highest level in comparison to the other synthesized derivatives but showed lesser inhibition as compared to streptomycin sulphate.
A further research on most active synthesized compounds as lead molecules may result in discovery of novel anticancer and antitubercular agents.
本研究描述了一系列2-(1-苯甲酰基-1H-苯并[d]咪唑-2-基硫代)-N-取代乙酰胺衍生物的合成、表征、体外抗菌和抗癌评估。还评估了合成衍生物对结核分枝杆菌H37Rv的体外抗结核活性。对在体外研究中发现具有活性的化合物在小鼠模型中进行体内抗结核活性评估，并评估其对重要分枝杆菌酶（即异柠檬酸裂解酶、泛酸合成酶和分支酸变位酶）的抑制作用。
与标准抗菌和抗真菌药物相比，化合物8、9和11在抗菌试验中表现为优秀的抗菌剂。抗癌活性结果显示，大多数衍生物对MCF7和HCT116细胞系的细胞毒性低于标准药物（他莫昔芬和5-氟尿嘧啶）。然而，化合物2（IC = 0.0047 μM/ml）和化合物10（IC = 0.0058 μM/ml）分别对MCF7和HCT116细胞系表现出最高的细胞毒性。体内抗结核活性结果表明，1.34 mg/kg的剂量对合成化合物是安全的。化合物的毒性剂量为5.67 mg/kg, 而致死剂量在小鼠体重的1.81至3.17 mg/kg之间变化。与其他合成衍生物相比，化合物18对所有三种分枝杆菌酶的抑制作用最强，但与硫酸链霉素相比抑制作用较小。
对最具活性的合成化合物作为先导分子进行进一步研究，可能会发现新型抗癌和抗结核药物。
