{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:35:24Z","timestamp":1791920124126,"version":"4.3.4"},"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T00:00:00Z","timestamp":1614124800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004457","name":"The World Academy of Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004457","id-type":"DOI","asserted-by":"publisher"}]},{"name":"African-German Network of Excellence in Science"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Carboxamides bearing sulphonamide functionality have been shown to exhibit significant lethal effect on <jats:italic>Plasmodium falciparum<\/jats:italic>, 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 <jats:italic>P<\/jats:italic>. <jats:italic>falciparum<\/jats:italic> N-myristoyltransferase, a confirmed drug target in the pathogen. Results revealed that sixteen new derivatives killed the parasite at single-digit micromolar concentration (IC<jats:sub>50<\/jats:sub> = 2.40\u20138.30 \u03bcM) and compounds <jats:bold>10b<\/jats:bold>, <jats:bold>10c<\/jats:bold>, <jats:bold>10d<\/jats:bold>, <jats:bold>10j<\/jats:bold> and <jats:bold>10o<\/jats:bold> scavenged DPPH radicals at IC<jats:sub>50<\/jats:sub>s (6.48, 8.49, 3.02, 6.44 and 4.32 \u03bcg\/mL respectively) comparable with 1.06 \u03bcg\/mL for ascorbic acid. Compound <jats:bold>10o<\/jats:bold> emerged as the most active of the derivatives to bind to the PfNMT with theoretical inhibition constant (<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub> = 0.09 \u03bcM) comparable to the reference ligand pyrazole-sulphonamide (<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub> = 0.01 \u03bcM). This study identifies compound <jats:bold>10o<\/jats:bold>, and this series in general, as potential antimalarial candidate with antioxidant activity which requires further attention to optimise activity.<\/jats:p>","DOI":"10.1371\/journal.pone.0243305","type":"journal-article","created":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T18:41:43Z","timestamp":1614192103000},"page":"e0243305","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":21,"title":["New sulphonamide pyrolidine carboxamide derivatives: Synthesis, molecular docking, antiplasmodial and antioxidant activities"],"prefix":"10.1371","volume":"16","author":[{"given":"Efeturi A.","family":"Onoabedje","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1620-5716","authenticated-orcid":true,"given":"Akachukwu","family":"Ibezim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uchechukwu C.","family":"Okoro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Batra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,2,24]]},"reference":[{"key":"pone.0243305.ref001","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1038\/nature09107","article-title":"Thousands of chemicals starting points for antimalarial lead identification","volume":"465","author":"FJ Gamo","year":"2010","journal-title":"Nature"},{"key":"pone.0243305.ref002","first-page":"1","article-title":"New developments in antimalarial target candidate and product profiles","volume":"16","author":"JN Burrows","year":"2017","journal-title":"Malaria J"},{"key":"pone.0243305.ref003","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1007\/s40265-018-0911-9","article-title":"Drugs in development for malaria","volume":"78","author":"EA Ashley","year":"2018","journal-title":"Drugs"},{"key":"pone.0243305.ref004","first-page":"1","article-title":"The past, present and future of antimalarial medicines","volume":"18","author":"EG Tse","year":"2019","journal-title":"Malaria J"},{"key":"pone.0243305.ref005","unstructured":"WHO Media Center. 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