Identification and validation of potent Mycobacterial proteasome inhibitor from Enamine library. Issue 19 (15th November 2022)

• Record Type: Journal Article
• Authors: Tyagi, Rashmi; Srivastava, Mitul; Singh, Baldeep; Sharma, Shingini; Pandey, Ramendra Pati; Asthana, Shailendra; Kumar, Dhruv; Raj, V. Samuel
• Is Part Of: Journal of biomolecular structure & dynamics. Volume 40:Issue 19(2022)
• Page Start: 8644
• Page End: 8654
• Publication Date: 2022-11-15
• Subjects: Tuberculosis -- Mycobacterial proteasome -- molecular dynamics -- molecular docking -- drug designing; Biomolecules -- Periodicals; Molecular structure -- Periodicals; Molecular Biology -- Periodicals; Biomechanics -- Periodicals; 572
• DOI: 10.1080/07391102.2021.1914173
• Languages: English
• ISSNs: 0739-1102

Abstract

Abstract: 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 ( in vitro susceptibility assay, enzyme inhibition assay and MTT assay). In silico outcome that two inhibiters were interacting at the active site pocket of receptor with high stability, was found to be very consistent with in vitro results. So it was conferred that compounds (Z1020863610, Z106766984) are potential lead for future process of drug development ( in vivo testing and clinical trials). Communicated by Ramaswamy H. Sarma