Synthesis and molecular modelling studies of novel sulphonamide derivatives as dengue virus 2 protease inhibitors.

Autor: Timiri AK; Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835215, Jharkhand, India., Selvarasu S; Centre for Advanced Study in Crystallography and Biophysics, University of Madras, Chennai 600 025, Tamil Nadu, India., Kesherwani M; Centre for Advanced Study in Crystallography and Biophysics, University of Madras, Chennai 600 025, Tamil Nadu, India., Vijayan V; Centre for Advanced Study in Crystallography and Biophysics, University of Madras, Chennai 600 025, Tamil Nadu, India., Sinha BN; Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835215, Jharkhand, India., Devadasan V; Centre for Advanced Study in Crystallography and Biophysics, University of Madras, Chennai 600 025, Tamil Nadu, India., Jayaprakash V; Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835215, Jharkhand, India. Electronic address: venkatesanj@bitmesra.ac.in.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2015 Oct; Vol. 62, pp. 74-82. Date of Electronic Publication: 2015 Jul 29.
DOI: 10.1016/j.bioorg.2015.07.005
Abstrakt: Development of antivirals for dengue is now based on rational approach targeting the enzymes involved in its life cycle. Among the targets available for inhibition of dengue virus, non-structural protein NS2B-NS3 protease is considered as a promising target for the development of anti-dengue agents. In the current study we have synthesized a series of 4-(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)benzene-1-sulphonamide derivatives and screened for DENV2 protease activity. Compounds 16 and 19 showed IC50 of DENV2 Protease activity with 48.2 and 121.9μM respectively. Molecular docking and molecular dynamic simulation studies were carried out to know the binding mode responsible for the activity. MD simulations revealed that, NS2B/NS3 protease was more stable when it binds with the active compound. Structure optimization of the lead compounds 16 and 19 and their co-crystallization studies are underway.
(Copyright © 2015 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: