Identification of starvation-mimetic bioactive phytocomponent from Withania somnifera using in-silico molecular modelling and flow cytometry-based analysis for the management of malaria

Multidrug resistance episodes in malaria increased from 3.9% to 20% from 2015 to 2019. Synchronizing the clinical manifestation in chronological sequence led to a unique impression on glucose demand (increased up to 100-fold) by the parasite-infected RBCs. Hence, restriction in the glucose uptake to...

Full description

Saved in:
Bibliographic Details
Published in:Journal of biomolecular structure & dynamics 2024-01, Vol.42 (1), p.528-549
Main Authors: Pradhan, Deepak, Biswasroy, Prativa, Kulkarni, Sharvari, Taliyan, Rajiv, Pradhan, Dilip Kumar, Bhola, Rajesh Kumar, Mahapatra, Sonali, Ghosh, Goutam, Rath, Goutam
Format: Article
Language:English
Subjects:
ADMET
Flow Cytometry
Glucose - metabolism
GLUT-1
Hemolysis
in-silico
Malaria
Malaria - drug therapy
PfHT
Plant Extracts - pharmacology
Withaferin A
Withania - chemistry
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Multidrug resistance episodes in malaria increased from 3.9% to 20% from 2015 to 2019. Synchronizing the clinical manifestation in chronological sequence led to a unique impression on glucose demand (increased up to 100-fold) by the parasite-infected RBCs. Hence, restriction in the glucose uptake to parasite-infected RBCs could be an alternative approach to conquer the global burden of malaria to a greater extent. A C28 steroidal lactone Withaferin A (WS-3) isolated from Withania somnifera leave extract shows better thermodynamically stable interactions with the glucose transporters (GLUT-1 and PfHT) to standard drugs metformin and lopinavir. MD simulations for a trajectory period of 100 ns reflect stable interactions with the interactive amino acid residues such as Pro141, Gln161, Gln282, Gln283, Trp388, Phe389, and Phe40, Asn48, Phe85, His168, Gln169, Asn311 which potentiating inhibitory activity of WS-3 against GLUT-1 and PfHT respectively. WS-3 was non-hemotoxic (%hemolysis
ISSN:0739-1102
1538-0254
DOI:10.1080/07391102.2023.2201855