Dr. APJ Kalam Research Lab, Department of Pharmaceutical Chemistry, SRM College of Pharmacy, SRM Institute of Science and Technology, Chengalpattu, Tamil Nadu, India.
Department of Biotechnology, Sastra Deemed to be University, Thanjavur, India.
J Biomol Struct Dyn. 2023;41(24):15165-15176. doi: 10.1080/07391102.2023.2227711. Epub 2023 Jun 22.
A series of halogenated chalcone derivatives were designed and developed for anti-tubercular activity. Novel molecules were designed and screening were performed using admetSAR, SwissADME, and Osiris Property Explorer. From the initial filter the top 10 compounds were docked using the Autodock tool 1.5.6. and the binding energies of the docked compounds were higher than the standard drugs Isoniazid.and Ethionamide. Based on the and docking results, the top halogenated chalcones were synthesized and characterized using FT-IR, mass spectrometry, H, and C NMR spectroscopy. The chalcones were further evaluated for anti-tubercular activity using MABA against the H37Rv strain. Among the series of compounds, DK12 and DK14 showed potent activity, with MICs of 0.8 µg/ml, in comparison with 1.6 µg/ml of the first-line drug Isoniazid. Further molecular dynamics simulations studies for 100 ns revealed that the key interaction with TYR 158 were observed in both DK12 and DK14 in the active site. The compound DK12 further showed significant interactions with PHE 149 and ARG 153 residues and is a hit molecule among the series. Further DK12 and DK14 does not show any significance toxicity. The compounds DK12 needs to be optimized and further investigation to be carried out against .Communicated by Ramaswamy H. Sarma.
一系列卤化查耳酮衍生物被设计和开发用于抗结核活性。使用 admetSAR、SwissADME 和 Osiris Property Explorer 进行了新分子的设计和筛选。从初始筛选中，使用 Autodock 工具 1.5.6 对前 10 种化合物进行对接，并且对接化合物的结合能高于标准药物异烟肼和乙胺丁醇。基于对接结果，合成了前卤化查耳酮，并使用 FT-IR、质谱、H 和 C NMR 光谱进行了表征。进一步使用 MABA 对 H37Rv 菌株评估了查耳酮的抗结核活性。在一系列化合物中，DK12 和 DK14 表现出较强的活性，MIC 为 0.8 μg/ml，与一线药物异烟肼的 1.6 μg/ml 相比。进一步进行 100 ns 的分子动力学模拟研究表明，在活性部位观察到与 TYR 158 的关键相互作用在 DK12 和 DK14 中都存在。化合物 DK12 进一步与 PHE 149 和 ARG 153 残基表现出显著的相互作用，是该系列中的一个命中分子。进一步的 DK12 和 DK14 没有表现出任何显著的毒性。需要对化合物 DK12 进行优化，并进一步针对结核分枝杆菌进行研究。由 Ramaswamy H. Sarma 传达。
