Open AccessNew sulphonamide pyrolidine carboxamide derivatives: Synthesis, molecular docking, antiplasmodial and antioxidant activities
Author(s) -
Efeturi A. Onoabedje,
Akachukwu Ibezim,
Uchechukwu C. Okoro,
Sanjay Batra
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0243305
Subject(s) - docking (animal) , carboxamide , stereochemistry , chemistry , plasmodium falciparum , antioxidant , dpph , pyrazole , ascorbic acid , affinities , combinatorial chemistry , malaria , biochemistry , biology , medicine , veterinary medicine , food science , immunology
Carboxamides bearing sulphonamide functionality have been shown to exhibit significant lethal effect on Plasmodium falciparum , the causative agent of human malaria. Here we report the synthesis of thirty-two new drug-like sulphonamide pyrolidine carboxamide derivatives and their antiplasmodial and antioxidant capabilities. In addition, molecular docking was used to check their binding affinities for homology modelled P . falciparum N-myristoyltransferase, a confirmed drug target in the pathogen. Results revealed that sixteen new derivatives killed the parasite at single-digit micromolar concentration (IC 50 = 2.40–8.30 μM) and compounds 10b , 10c , 10d , 10j and 10o scavenged DPPH radicals at IC 50 s (6.48, 8.49, 3.02, 6.44 and 4.32 μg/mL respectively) comparable with 1.06 μg/mL for ascorbic acid. Compound 10o emerged as the most active of the derivatives to bind to the PfNMT with theoretical inhibition constant ( K i = 0.09 μM) comparable to the reference ligand pyrazole-sulphonamide ( K i = 0.01 μM). This study identifies compound 10o , and this series in general, as potential antimalarial candidate with antioxidant activity which requires further attention to optimise activity.