{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:54:25Z","timestamp":1792122865285,"version":"4.4.0"},"reference-count":39,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,14]],"date-time":"2021-02-14T00:00:00Z","timestamp":1613260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The in vitro activity of L. donovani (promastigotes, axenic amastigotes and intracellular amastigotes in THP1 cells) and T. brucei, from the fractions obtained from the hydroalcoholic extract of the aerial part of Hypericum afrum and the isolated compounds, has been evaluated. The chloroform, ethyl acetate and n-butanol extracts showed significant antitrypanosomal activity towards T. brucei, with IC50 values of 12.35, 13.53 and 12.93 \u00b5g\/mL and with IC90 values of 14.94, 19.31 and 18.67 \u00b5g\/mL, respectively. The phytochemical investigation of the fractions led to the isolation and identification of quercetin (1), myricitrin (2), biapigenin (3), myricetin (4), hyperoside (5), myricetin-3-O-\u03b2-d-galactopyranoside (6) and myricetin-3\u2019-O-\u03b2-d-glucopyranoside (7). Myricetin-3\u2019-O-\u03b2-d-glucopyranoside (7) has been isolated for the first time from this genus. The chemical structures were elucidated by using comprehensive one- and two-dimensional nuclear magnetic resonance (1D and 2D NMR) spectroscopic data, as well as high-resolution electrospray ionization mass spectrometry (HR-ESI\u2013MS). These compounds have also been evaluated for their antiprotozoal activity. Quercetin (1) and myricetin (4) showed noteworthy activity against T. brucei, with IC50 and IC90 values of 7.52 and 5.71 \u00b5M, and 9.76 and 7.97 \u00b5M, respectively. The T. brucei hexokinase (TbHK1) enzyme was further explored as a potential target of quercetin and myricetin, using molecular modeling studies. This proposed mechanism assists in the exploration of new candidates for novel antitrypanosomal drugs.<\/jats:p>","DOI":"10.3390\/molecules26041009","type":"journal-article","created":{"date-parts":[[2021,2,14]],"date-time":"2021-02-14T08:53:56Z","timestamp":1613292836000},"page":"1009","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Proposed Mechanism for the Antitrypanosomal Activity of Quercetin and Myricetin Isolated from Hypericum afrum Lam.: Phytochemistry, In Vitro Testing and Modeling Studies"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1396-0719","authenticated-orcid":false,"given":"Farida","family":"Larit","sequence":"first","affiliation":[{"name":"D\u00e9partement de Chimie, Facult\u00e9 des Sciences Exactes, Universit\u00e9 des Fr\u00e8res Mentouri Constantine 1, Constantine 25000, Algeria"},{"name":"Department of BioMolecular Sciences, Division of Medicinal Chemistry, University of Mississippi, University, MS 38677, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2394-021X","authenticated-orcid":false,"given":"Khaled M.","family":"Elokely","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Institute for Computational Molecular Science, Temple University, Philadelphia, PA 19122, USA"},{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manal A.","family":"Nael","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Institute for Computational Molecular Science, Temple University, Philadelphia, PA 19122, USA"},{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samira","family":"Benyahia","sequence":"additional","affiliation":[{"name":"Laboratoire de Synth\u00e8se Organique, Mod\u00e9lisation et Optimisation des Proc\u00e8des (LOMOP), Universit\u00e9 Badji Mokhtar, Annaba 23000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5064-2381","authenticated-orcid":false,"given":"Francisco","family":"Le\u00f3n","sequence":"additional","affiliation":[{"name":"Department of BioMolecular Sciences, Division of Medicinal Chemistry, University of Mississippi, University, MS 38677, USA"},{"name":"Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Cutler","sequence":"additional","affiliation":[{"name":"Department of BioMolecular Sciences, Division of Medicinal Chemistry, University of Mississippi, University, MS 38677, USA"},{"name":"Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9179-4373","authenticated-orcid":false,"given":"Mohammed M.","family":"Ghoneim","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, College of Pharmacy, AlMaarefa University, Ad Diriyah, Riyadh 13713, Saudi Arabia"},{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Cairo 11371, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,14]]},"reference":[{"key":"ref_1","unstructured":"(2020, December 23). 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