{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T19:12:22Z","timestamp":1788981142277,"version":"build-2803163510"},"reference-count":45,"publisher":"International Association of Physical Chemists (IAPC)","license":[{"start":{"date-parts":[[2026,5,24]],"date-time":"2026-05-24T00:00:00Z","timestamp":1779580800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ADMET DMPK"],"abstract":"<jats:p>Background and purpose New Delhi Metallo beta-lactamase-1 (NDM-1) is a zinc-dependent enzyme that confers resistance to several antibiotics; therefore, there is an urgent requirement for effective inhibitors. Captopril has been exploited as a scaffold in the design of NDM-1 inhibitors; however, a comparative evaluation of these derivatives from structure activity relationship perspective has not been conducted. This review aimed to evaluate captopril-derived NDM-1 inhibitors and to identify possible structure-activity relationships that govern their NDM-1 inhibitory action. Experimental approach: The literature was searched in a structured manner using scholarly databases to locate original studies that reported captopril derivatives and evaluated them in vitro against NDM-1 with the explicit reporting of the inhibitory concen\u00adtration values (IC50). Eligible studies were filtered using predefined criteria and analysed using a qualitative approach, because heterogeneity in assay conditions and experimental methods prevented a direct quantitative comparison across studies. Important findings: The activity of captopril derivatives depends on the free thiol group (masking it reduces activity), with stereochemistry governing optimal binding orientation within the NDM-1 active site, hydrophobic substitutions enhance activity only within steric limits, and the carboxylate motif serves as a secondary anchoring feature. Conclusion: Captopril emerges as a promising scaffold for NDM-1 inhibitors and reveals significant structural features associated with NDM-1 inhibitors. Despite limited in vivo data and heterogeneity in assay conditions, the findings provide a rational framework for optimizing captopril-inspired NDM-1 inhibitors.<\/jats:p>","DOI":"10.5599\/admet.3304","type":"journal-article","created":{"date-parts":[[2026,5,24]],"date-time":"2026-05-24T12:17:30Z","timestamp":1779625050000},"source":"Crossref","is-referenced-by-count":0,"title":["Structure-activity relationship of captopril derivatives as New Delhi metallo beta-lactamase 1 inhibitors"],"prefix":"10.5599","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2232-5928","authenticated-orcid":false,"given":"Ikhlas","family":"Jarrar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3564","published-online":{"date-parts":[[2026,5,24]]},"reference":[{"key":"180943","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.0c00863"},{"key":"180944","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00774-09"},{"key":"180945","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(10)70143-2"},{"key":"180946","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.113667"},{"key":"180947","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00037-09"},{"key":"180948","doi-asserted-by":"publisher","DOI":"10.3201\/eid1710.110655"},{"key":"180949","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S280977"},{"key":"180950","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06839-1"},{"key":"180951","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-011-1055-9"},{"key":"180952","doi-asserted-by":"publisher","DOI":"10.1002\/phar.4629"},{"key":"180953","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.8b00247"},{"key":"180954","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.581001"},{"key":"180955","unstructured":"[13] B.A. Fomda, A. Khan, D. Zahoor. NDM-1 (New Delhi Metallo beta lactamase-1) producing Gram-negative bacilli: emergence & clinical implications. Indian Journal of Medical Research 140 (2014) 672-678. https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4311323\/"},{"key":"180956","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23010197"},{"key":"180957","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2013.03.031"},{"key":"180958","doi-asserted-by":"publisher","DOI":"10.1089\/mdr.2019.0315"},{"key":"180959","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.201402268"},{"key":"180960","doi-asserted-by":"publisher","DOI":"10.1039\/C5CC02594J"},{"key":"180961","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b00911"},{"key":"180962","doi-asserted-by":"publisher","DOI":"10.1111\/jam.13085"},{"key":"180963","doi-asserted-by":"publisher","DOI":"10.1007\/s00775-020-01794-z"},{"key":"180964","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-443-18611-0.00036-X"},{"key":"180965","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c01755"},{"key":"180966","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12406"},{"key":"180967","doi-asserted-by":"publisher","DOI":"10.1055\/s-0042-1751317"},{"key":"180968","unstructured":"[26] RCSB Protein Data Bank. Crystal structure of NDM-1 in complex with L-captopril. https:\/\/www.rcsb.org\/structure\/5ZIO (accessed January 17, 2026)"},{"key":"180969","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2018.11.035"},{"key":"180970","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.7b00058"},{"key":"180971","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.7b01299"},{"key":"180972","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2016.02.007"},{"key":"180973","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0324836"},{"key":"180974","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmgm.2018.06.004"},{"key":"180975","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23031834"},{"key":"180976","doi-asserted-by":"publisher","DOI":"10.7150\/thno.56205"},{"key":"180977","doi-asserted-by":"publisher","DOI":"10.1021\/ja303579d"},{"key":"180978","unstructured":"[36] T. Yu, A. Malik, N. Anuwongcharoen, W. Eiamphungporn, C. Nantasenamat, T. Piacham. Towards combating antibiotic resistance by exploring the quantitative structure-activity relationship of NDM-1 inhibitors. EXCLI Journal 21 (2022) 1331-1341. https:\/\/doi.org\/10.17179\/excli2022-5380"},{"key":"180979","unstructured":"[37] D.T. King. Protecting our beta-lactam antibiotic assets: structural investigation of beta-lactamases. PhD Thesis, University of British Columbia, Vancouver, Canada, 2016. https:\/\/doi.org\/10.14288\/1.0222998"},{"key":"180980","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2020.115902"},{"key":"180981","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01335-15"},{"key":"180982","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2013.10.068"},{"key":"180983","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.8b00366"},{"key":"180984","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5c00750"},{"key":"180985","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2024.116140"},{"key":"180986","doi-asserted-by":"publisher","DOI":"10.1038\/nchem.2110"},{"key":"180987","doi-asserted-by":"publisher","DOI":"10.1021\/jm400769b"}],"container-title":["ADMET and DMPK"],"original-title":[],"link":[{"URL":"https:\/\/pub.iapchem.org\/ojs\/index.php\/admet\/article\/download\/3304\/2914","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pub.iapchem.org\/ojs\/index.php\/admet\/article\/download\/3304\/3038","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pub.iapchem.org\/ojs\/index.php\/admet\/article\/download\/3304\/2913","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T18:51:43Z","timestamp":1788979903000},"score":1,"resource":{"primary":{"URL":"https:\/\/pub.iapchem.org\/ojs\/index.php\/admet\/article\/view\/3304"}},"subtitle":["Review paper"],"short-title":[],"issued":{"date-parts":[[2026,5,24]]},"references-count":45,"URL":"https:\/\/doi.org\/10.5599\/admet.3304","relation":{},"ISSN":["1848-7718"],"issn-type":[{"value":"1848-7718","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,24]]},"article-number":"3304"}}