{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T17:31:49Z","timestamp":1770744709441,"version":"3.49.0"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,9,7]],"date-time":"2020-09-07T00:00:00Z","timestamp":1599436800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Methionine aminopeptidase 1 (MetAP1) is a target for drug discovery against many adversaries and a potential antileishmanial target for its role in N\u2010terminal methionine processing. As an effort towards new inhibitor discovery against methionine aminopeptidase 1 from<jats:italic>Leishmania donovani<\/jats:italic>(<jats:italic>Ld<\/jats:italic>MetAP1), we have synthesized a series of quinoline\u2010based hybrids, that is (Z)\u20105\u2010((Z)\u2010benzylidine)\u20102\u2010(quinolin\u20103\u2010ylimino)thiazolidin\u20104\u2010ones (QYT\u20104a\u2010i) whose in vitro screening led to the discovery of a novel inhibitor molecule (QYT\u20104h) against<jats:italic>Ld<\/jats:italic>MetAP1. The compound QYT\u20104h showed nearly 20\u2010fold less potency for human MetAP1 and had drug\u2010like features. Time\u2013course kinetic assays suggested QYT\u20104h acting through a competitive mode by binding to the metal\u2010activated catalytic site. Notably, QYT\u20104h was most potent against the physiologically relevant Mn(II) and Fe(II) supplemented forms of<jats:italic>Ld<\/jats:italic>MetAP1 and less potent against Co(II) supplemented form. Surface plasmon resonance and fluorescence spectroscopy demonstrated high affinity of QYT\u20104h for<jats:italic>Ld<\/jats:italic>MetAP1. Through molecular modelling and docking studies, we found QYT\u20104h binding at the<jats:italic>Ld<\/jats:italic>MetAP1 catalytic pocket occupying both the catalytic and substrate binding sites mostly with hydrogen bonding and hydrophobic interactions which provide structural basis for its promising potency. These results demonstrate the feasibility of employing small\u2010molecule inhibitors for selective targeting of<jats:italic>Ld<\/jats:italic>MetAP1 which may find use to effectively eliminate leishmaniasis.<\/jats:p>","DOI":"10.1111\/cbdd.13783","type":"journal-article","created":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T16:13:42Z","timestamp":1597940022000},"page":"315-324","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Development of quinoline\u2010based hybrid as inhibitor of methionine aminopeptidase 1 from<i>Leishmania donovani<\/i>"],"prefix":"10.1111","volume":"97","author":[{"given":"Saleem Yousuf","family":"Bhat","sequence":"first","affiliation":[{"name":"Department of Biotechnology and Bioinformatics, School of Life Sciences University of Hyderabad Hyderabad 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