Synthesis and inhibition studies towards the discovery of benzodiazepines as potential antimalarial compounds.
Apicoplast
Benzodiazepine
IPP synthesis
Malaria
PfDXR inhibitor
Plasmodium
Journal
Experimental parasitology
ISSN: 1090-2449
Titre abrégé: Exp Parasitol
Pays: United States
ID NLM: 0370713
Informations de publication
Date de publication:
Dec 2022
Dec 2022
Historique:
received:
13
07
2022
revised:
04
10
2022
accepted:
18
10
2022
pubmed:
8
11
2022
medline:
30
11
2022
entrez:
7
11
2022
Statut:
ppublish
Résumé
The target-based discovery of therapeutics against apicoplast, an all-important organelle is an overriding perspective. MEP pathway, an accredited drug target provides an insight into the importance of apicoplast in the survival of the parasite. In this study, we present the rational design strategy employing sustainable catalysis for the synthesis of benzodiazepine (BDZ) conformers followed by their biological evaluation as prospective inhibitors against the potential target of the IPP pathway, 1-deoxy-D-xylulose-5-phosphatereductoisomerase (DXR). The study reported the inhibitory profile of 8c and 6d against the quintessential step of the only drug target in the erythrocytic stages of parasite development. The potential compounds were identified to represent a novel class of inhibitors that serve as the lead molecules to impede the pathway and further affect the survival of the parasite.
Identifiants
pubmed: 36342006
pii: S0014-4894(22)00205-3
doi: 10.1016/j.exppara.2022.108411
pii:
doi:
Substances chimiques
Antimalarials
0
Benzodiazepines
12794-10-4
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
108411Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare no conflict of interests.