State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
Bioorg Med Chem Lett. 2012 May 1;22(9):3044-9. doi: 10.1016/j.bmcl.2012.03.079. Epub 2012 Mar 28.
In this study, a novel benzothiazol- and benzooxazol-2-amine scaffold with antibacterial activity was designed and synthesized. Preliminary structure-activity relationship analysis displayed that compound 8t with a 5,6-difluorosubstituted benzothiazole was found to be a potent inhibitor of Gram-positive pathogens, and exhibited some potential against drug-resistant bacteria and without cytotoxicity in therapeutic concentrations. In addition, molecular docking studies indicated that Staphylococcus aureus methionyl-tRNA synthetase might be the possible target of these compounds. Taken together, the present study provides an effective entry to the synthesis of a good lead for subsequent optimization and a new small molecule candidate drug for antibacterial therapeutics.
在这项研究中，设计并合成了一种具有抗菌活性的新型苯并噻唑-和苯并恶唑-2-胺支架。初步的结构-活性关系分析表明，带有 5,6-二氟取代苯并噻唑的化合物 8t 被发现是革兰氏阳性病原体的有效抑制剂，并且对耐药菌具有一定的潜力，并且在治疗浓度下没有细胞毒性。此外，分子对接研究表明，金黄色葡萄球菌甲硫氨酰-tRNA 合成酶可能是这些化合物的可能靶标。综上所述，本研究为随后的优化提供了一种有效的方法，为抗菌治疗提供了一种新的小分子候选药物。
