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Numerous studies on snake viperid venoms found that metalloproteinases play a significant role in the pathophysiology of hemorrhage that occurs on envenomation. Preclinical studies using vitro and in vivo protocols investigated natural compounds and viperid snake venoms, evaluating the enzymatic, procoagulant, hemorrhagic, edematogenic, myotoxic, and lethal activities. Many studies focused on Bothrops venoms and ascribed that angiorrhexis and hemorrhage resulted from the metalloproteinase action on collagen in the basal lamina. This effect resulted in a combined action with phospholipase A2 and hyaluronidase, inducing hemorrhage, edema, and necrosis. Due to the lack of efficient antivenoms in remote areas, traditional native plant treatments remain common, especially in the Amazon. Our group studied plant extracts, isolated compounds, and lapachol synthetic derivative analogs with selective inhibition for Bothrops venom proteolytic and hemorrhagic activity and devoid of phospholipase activity. We highlight those new synthetic naphthoquinones which inhibit snake venom metalloproteinases and that are devoid of other venom enzyme inhibition. This review shows the potential use of snake venom effects, mainly Bothrops venom metalloproteinase activity, as a tool to identify and develop new active molecules against hemorrhagic effects.<\/jats:p>","DOI":"10.3390\/ijms26093950","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T20:24:52Z","timestamp":1745353492000},"page":"3950","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Plant-Derived Lapachol Analogs as Selective Metalloprotease Inhibitors Against Bothrops Venom: A Review"],"prefix":"10.3390","volume":"26","author":[{"given":"Paulo A.","family":"Melo","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Farmacologia das Toxinas, Programa de P\u00f3s-Gradua\u00e7\u00e3o em Farmacologia e Qu\u00edmica Medicinal, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e2mella Dourila","family":"Nogueira-Souza","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Farmacologia das Toxinas, Programa de P\u00f3s-Gradua\u00e7\u00e3o em Farmacologia e Qu\u00edmica Medicinal, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayara Amorim","family":"Romanelli","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Farmacologia das Toxinas, Programa de P\u00f3s-Gradua\u00e7\u00e3o em Farmacologia e Qu\u00edmica Medicinal, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9576-6310","authenticated-orcid":false,"given":"Marcelo A.","family":"Strauch","sequence":"additional","affiliation":[{"name":"Departamento de Ci\u00eancias Fisiol\u00f3gicas, Instituto de Ci\u00eancias Biol\u00f3gicas e da Sa\u00fade, Universidade Federal Rural do Rio de Janeiro, Serop\u00e9dica 23890-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo de Oliveira","family":"Cesar","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Farmacologia das Toxinas, Programa de P\u00f3s-Gradua\u00e7\u00e3o em Farmacologia e Qu\u00edmica Medicinal, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, Brazil"},{"name":"Instituto Vital Brazil, Niter\u00f3i 24230-410, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1657-1356","authenticated-orcid":false,"given":"Marcos","family":"Monteiro-Machado","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Farmacologia das Toxinas, Programa de P\u00f3s-Gradua\u00e7\u00e3o em Farmacologia e Qu\u00edmica Medicinal, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando Chagas","family":"Patr\u00e3o-Neto","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Farmacologia das Toxinas, Programa de P\u00f3s-Gradua\u00e7\u00e3o em Farmacologia e Qu\u00edmica Medicinal, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina R.","family":"Gonsalez","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Campus Maca\u00e9, Rio de Janeiro 21941-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8824-5701","authenticated-orcid":false,"given":"Nilton Ghiotti","family":"Siqueira","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias da Sa\u00fade e do Desporto, Universidade Federal do Acre, Rio Branco 69920-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar","family":"Schaeffer","sequence":"additional","affiliation":[{"name":"Instituto de Pesquisas de Produtos Naturais Walter Mors, Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo R. R.","family":"Costa","sequence":"additional","affiliation":[{"name":"Instituto de Pesquisas de Produtos Naturais Walter Mors, Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3200-0318","authenticated-orcid":false,"given":"Alcides J. M.","family":"da Silva","sequence":"additional","affiliation":[{"name":"Instituto de Pesquisas de Produtos Naturais Walter Mors, Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Guti\u00e9rrez, J.M., Theakston, R.D.G., and Warrell, D.A. (2006). Confronting the Neglected Problem of Snake Bite Envenoming: The Need for a Global Partnership. 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