Tyagi Rashmi, Srivastava Mitul, Singh Baldeep, Sharma Shingini, Pandey Ramendra Pati, Asthana Shailendra, Kumar Dhruv, Raj V Samuel
Centre for Drug Design Discovery and Development (C4D), SRM University, Delhi NCR, Sonepat, India.
Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, India.
J Biomol Struct Dyn. 2022;40(19):8644-8654. doi: 10.1080/07391102.2021.1914173. Epub 2021 May 6.
As a consequence of present status of tuberculosis (TB) it is the obligation to develop novel targets and potential drugs so that rate of drug resistant TB can be declined. Mycobacterium proteasome is considered to be significant target for the purpose of drug designing as it is responsible for resisting the effect of NO (nitric oxide) immune system defence mechanism against the bacterial cells. Small compounds library from Enamine database has already been tested using virtual screening and molecular docking studies. Further a reanalysis with two picked out significant compounds Z1020863610, Z106766984 was carried out using molecular dynamic simulation studies and in vitro validations ( susceptibility assay, enzyme inhibition assay and MTT assay). outcome that two inhibiters were interacting at the active site pocket of receptor with high stability, was found to be very consistent with results. So it was conferred that compounds (Z1020863610, Z106766984) are potential lead for future process of drug development ( testing and clinical trials).Communicated by Ramaswamy H. Sarma.
鉴于结核病的现状，开发新的靶点和潜在药物以降低耐药结核病的发病率是当务之急。分枝杆菌蛋白酶体被认为是药物设计的重要靶点，因为它负责抵抗一氧化氮（NO）免疫系统对细菌细胞的防御机制。来自Enamine数据库的小分子化合物库已经通过虚拟筛选和分子对接研究进行了测试。进一步使用分子动力学模拟研究和体外验证（药敏试验、酶抑制试验和MTT试验）对挑选出的两种重要化合物Z1020863610、Z106766984进行了重新分析。结果发现，两种抑制剂在受体的活性位点口袋处具有高度稳定性的相互作用，这与结果非常一致。因此，可以认为化合物（Z1020863610、Z106766984）是未来药物开发过程（测试和临床试验）的潜在先导物。由拉马斯瓦米·H·萨尔马传达。
