Purakkel Umadevi Kizhakke, Praveena Ganji, Madabhushi Valli Y, Jadav Surender Singh, Prakasham Reddy Shetty, Dasugari Varakala Saiprasad Goud, Sriram Dharmarajan, Blanch Ewan W, Maniam Subashani
Applied Chemistry and Environmental Science, STEM College, RMIT University, Melbourne, Victoria 3001, Australia.
Organic Synthesis and Process Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
ACS Omega. 2024 Feb 19;9(8):8846-8861. doi: 10.1021/acsomega.3c06324. eCollection 2024 Feb 27.
The rational design of novel thiazolo[2,3-][1,2,4]triazole derivatives was carried out based on previously identified antitubercular hit molecule H127 for discovering potent compounds showing antimicrobial activity. The designed compounds were screened for their binding efficacies against the antibacterial drug target enoyl-[acyl-carrier-protein] reductase, followed by prediction of drug-likeness and ADME properties. The designed analogues were chemically synthesized, characterized by spectroscopic techniques, followed by evaluation of antimicrobial activity against bacterial and fungal strains, as well as antitubercular activity against and strains. Among the synthesized compounds, five compounds, , , , and , revealed antimicrobial activity, albeit with differential potency against various microbial strains. Compounds and were the most active against (MIC: 8 μg/mL), while compounds and showed the highest activity against (MIC: 16 μg/mL), whereas compounds , and displayed activities against (MIC: 16 μg/mL). Meanwhile, compounds and depicted activities against (MIC: 16 μg/mL) and compound showed antifungal activity against (MIC: 32 μg/mL). The current study has identified two broad-spectrum antibacterial hit compounds ( and ). Further structural investigation on these molecules is underway to enhance their potency.
基于先前鉴定出的抗结核先导分子H127，开展了新型噻唑并[2,3 - ][1,2,4]三唑衍生物的合理设计，以发现具有抗菌活性的强效化合物。对设计的化合物针对抗菌药物靶点烯酰-[酰基载体蛋白]还原酶的结合效力进行筛选，随后预测其类药性质和药物代谢动力学性质。对设计的类似物进行化学合成，通过光谱技术进行表征，接着评估其对细菌和真菌菌株的抗菌活性以及对结核分枝杆菌菌株和的抗结核活性。在合成的化合物中，有5种化合物，即、、、和，显示出抗菌活性，尽管对各种微生物菌株的效力有所不同。化合物和对（最低抑菌浓度：8 μg/mL）活性最强，而化合物和对（最低抑菌浓度：16 μg/mL）表现出最高活性，化合物、和对（最低抑菌浓度：16 μg/mL）有活性。同时，化合物和对（最低抑菌浓度：16 μg/mL）有活性，化合物对（最低抑菌浓度：32 μg/mL）表现出抗真菌活性。当前研究已鉴定出两种广谱抗菌先导化合物（和）。正在对这些分子进行进一步的结构研究以提高其效力。
