Exploring the structural aspects of ureido-amino acid-based APN inhibitors: a validated comparative multi-QSAR modelling study

Abstract

The zinc-dependent enzyme aminopeptidase N (APN) is a member of the M1 metalloenzyme family. The multi-functionality of APN as a peptidase, a receptor and a signalling molecule has provided it the access to influence a number of disease conditions namely viral diseases, angiogenesis, cellular metastasis and invasion including different cancer conditions. Hence, the development of potent APN inhibitors is a possible route for the treatment of diseases related to the activity of APN. In this study, different QSAR approaches have been adopted to identify the structural features of a group of hydroxamate-based ureido-amino acid derivative APN inhibitors. This study was able to identify different constitutional aspects of these APN inhibitors which are important for their inhibitory potency. Additionally, some of these observations were also aligned with the observations of previously performed QSAR studies conducted on different APN inhibitors. Therefore, the results of this study may help to design potent and effective APN inhibitors in the future. ARTICLE HISTORY

Protease targeted COVID-19 drug discovery and its challenges: Insight into viral main protease (Mpro) and papain-like protease (PLpro) inhibitors

“…Diverse approaches have also been made in order get insights into the mechanism of these proteases and to inhibit their functions but still there has been a lot of groundwork to be done for drug discovery and development against these targets. This study, as a part of rational drug design and discovery 9-10, 34 , 35 , 36 , 37 , aims to sketch out the current status of SARS-CoV-2 protease inhibitors based drug discovery. We also try to provide a new insight into coronavirus protease structural biology and discuss the challenges in the development of effective as well as drug like protease inhibitors.…”

Chemical-informatics approach to COVID-19 drug discovery: Monte Carlo based QSAR, virtual screening and molecular docking study of some in-house molecules as papain-like protease (PLpro) inhibitors

“…Here, the virtual screening has fostered the application of drug design to the SARS-CoV-2 targets. This current communication, a component of our rational drug design and discovery headway (Adhikari et al, 2017;Amin et al, 2018;Banerjee et al, 2020;Dutta et al, 2019;Halder et al, 2013), we propounded mathematical modelling workflow based on Monte Carlo optimization and other approaches which further leads to the screening of possible SARS-CoV-2 PLpro inhibitors (Figure 1).…”