{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:11:51Z","timestamp":1791475911461,"version":"4.3.4"},"reference-count":69,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2018,10,16]],"date-time":"2018-10-16T00:00:00Z","timestamp":1539648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005278","name":"Universidad de Antioquia","doi-asserted-by":"publisher","award":["CODI-CIQF-217"],"award-info":[{"award-number":["CODI-CIQF-217"]}],"id":[{"id":"10.13039\/501100005278","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["CNS-1006860, EPS-1006860, EPS-0919443, and CHE-1726332"],"award-info":[{"award-number":["CNS-1006860, EPS-1006860, EPS-0919443, and CHE-1726332"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007828","name":"Kansas Bioscience Authority","doi-asserted-by":"publisher","award":["Institute of Computational Comparative Medicine (ICCM) and the Nanotechnology Innovation Center of Kansas State University"],"award-info":[{"award-number":["Institute of Computational Comparative Medicine (ICCM) and the Nanotechnology Innovation Center of Kansas State University"]}],"id":[{"id":"10.13039\/100007828","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Most of the snakebite envenomations in Central and South America are caused by species belonging to Bothrops genus. Their venom is composed mainly by zinc-dependent metalloproteinases, responsible of the hemorrhage characteristic of these envenomations. The aim of this study was to determine the inhibitory ability of ten flavonoids on the in-vitro proteolytic activity of Bothrops atrox venom and on the hemorrhagic, edema-forming and myonecrotic activities of Batx-I, the most abundant metalloproteinase isolated from this venom. Myricetin was the most active compound, exhibiting an IC     50     value of 150    \u03bc   M and 1021    \u03bc   M for the inhibition of proteolytic and hemorrhagic activity, respectively. Independent injection experiments, with a concentration of 1600    \u03bc   M of myricetin administered locally, immediately after toxin injection, demonstrated a reduction of     28 \u00b1 6 %     in the hemorrhagic lesion. Additionally, myricetin at concentrations 800, 1200 and 1600    \u03bc   M promoted a reduction in plasma creatine kinase activity induced by Batx-I of     21 \u00b1 2 %    ,     60 \u00b1 5 %     and     63 \u00b1 2 %    , respectively. Molecular dynamics simulations coupled with the adaptive biasing method suggest that myricetin can bind to the metalloproteinase active site via formation of hydrogen bonds between the hydroxyl groups 3\u2019, 4\u2019 and 5\u2019 of the benzyl moiety and amino acid Glu143 of the metalloproteinase. The hydroxyl substitution pattern of myricetin appears to be essential for its inhibitory activity. Based on this evidence, myricetin constitutes a candidate for the development of inhibitors to reduce local tissue damage in snakebite envenomations.<\/jats:p>","DOI":"10.3390\/molecules23102662","type":"journal-article","created":{"date-parts":[[2018,10,16]],"date-time":"2018-10-16T11:07:51Z","timestamp":1539688071000},"page":"2662","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Inhibition of a Snake Venom Metalloproteinase by the Flavonoid Myricetin"],"prefix":"10.3390","volume":"23","author":[{"given":"Lina","family":"Preciado","sequence":"first","affiliation":[{"name":"Programa de Ofidismo\/Escorpionismo, Facultad de Ciencias Farmac\u00e9uticas y Alimentarias, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medell\u00edn 050010, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Comer","sequence":"additional","affiliation":[{"name":"Institute of Computational Comparative Medicine, Kansas State University, Manhattan, KS 66506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitelbina","family":"N\u00fa\u00f1ez","sequence":"additional","affiliation":[{"name":"Programa de Ofidismo\/Escorpionismo, Facultad de Ciencias Farmac\u00e9uticas y Alimentarias, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medell\u00edn 050010, Colombia"},{"name":"Escuela de Microbiolog\u00eda, Universidad de Antioquia, UdeA, Calle 70 No. 52-21, Medell\u00edn 050010, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Rey-S\u00faarez","sequence":"additional","affiliation":[{"name":"Programa de Ofidismo\/Escorpionismo, Facultad de Ciencias Farmac\u00e9uticas y Alimentarias, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medell\u00edn 050010, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Perea\u00f1ez","sequence":"additional","affiliation":[{"name":"Programa de Ofidismo\/Escorpionismo, Facultad de Ciencias Farmac\u00e9uticas y Alimentarias, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medell\u00edn 050010, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17063","DOI":"10.1038\/nrdp.2017.63","article-title":"Snakebite envenoming","volume":"3","author":"Calvete","year":"2017","journal-title":"Nat. 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