Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia.
Department of Biotechnology and Food Technology, Durban University of Technology, Durban, South Africa.
J Enzyme Inhib Med Chem. 2021 Dec;36(1):1472-1487. doi: 10.1080/14756366.2021.1919889.
A series of 1,2,3-trisubstituted indolizines (, and ) were screened for whole-cell anti-tubercular activity against the susceptible H37Rv and multidrug-resistant (MDR) (MTB) strains. Compounds , , and were active against the H37Rv-MTB strain with minimum inhibitory concentration (MIC) ranging from 4 to 32 µg/mL, whereas the indolizines with ethyl ester group at the 4-position of the benzoyl ring also exhibited anti-MDR-MTB activity (MIC = 16-64 µg/mL). docking study revealed the enoyl-acyl carrier protein reductase (InhA) and anthranilate phosphoribosyltransferase as potential molecular targets for the indolizines. The X-ray diffraction analysis of the compound was also carried out. Further, a safety study ( and ) demonstrated no toxicity for these compounds. Thus, the indolizines warrant further development and may represent a novel promising class of InhA inhibitors and multi-targeting agents to combat drug-sensitive and drug-resistant MTB strains.
我们筛选了一系列 1,2,3-三取代的吲唑类化合物（、和），以评估它们对结核分枝杆菌（MTB）敏感株和耐多药株（MDR）的全细胞抗结核活性。化合物、和对 H37Rv-MTB 株具有活性，最低抑菌浓度（MIC）范围为 4 至 32μg/mL，而苯甲酰环 4 位带有乙酯基团的吲唑类化合物也表现出抗 MDR-MTB 活性（MIC=16-64μg/mL）。对接研究表明，烯酰基辅酶 A 还原酶（InhA）和邻氨基苯甲酸磷酸核糖基转移酶是吲唑类化合物的潜在分子靶标。还对化合物进行了 X 射线衍射分析。此外，安全性研究（和）表明这些化合物没有毒性。因此，吲唑类化合物值得进一步开发，它们可能代表一类新型的 InhA 抑制剂和多靶点药物，用于对抗敏感和耐药的 MTB 菌株。
