{"id":484,"date":"2024-06-07T08:00:00","date_gmt":"2024-06-07T08:00:00","guid":{"rendered":"https:\/\/projekti.imi.hr\/biomoltox\/?p=484"},"modified":"2024-10-02T10:07:20","modified_gmt":"2024-10-02T10:07:20","slug":"evaluation-of-anticholinesterase-activity-of-the-fungicides-mefentrifluconazole-and-pyraclostrobin","status":"publish","type":"post","link":"https:\/\/projekti.imi.hr\/biomoltox\/2024\/06\/07\/evaluation-of-anticholinesterase-activity-of-the-fungicides-mefentrifluconazole-and-pyraclostrobin\/","title":{"rendered":"Evaluation of Anticholinesterase Activity of the Fungicides Mefentrifluconazole and Pyraclostrobin"},"content":{"rendered":"\n<p><strong>Autori:\u00a0<\/strong>Dora Koli\u0107, Goran \u0160inko<\/p>\n\n\n\n<p><strong>Sa\u017eetak rada<\/strong><br>Triazoles are compounds with various biological activities, including fungicidal action. They became popular through cholinesterase studies after the successful synthesis of the dual binding femtomolar triazole inhibitor of acetylcholinesterase (AChE, EC 3.1.1.7) by Sharpless et al. via\u00a0<em>in situ<\/em>\u00a0click chemistry. Here, we evaluate the anticholinesterase effect of the first isopropanol triazole fungicide mefentrifluconazole (Ravystar<sup>\u00ae<\/sup>), developed to overcome fungus resistance in plant disease management. Mefentrifluconazole is commercially available individually or in a binary fungicidal mixture, i.e., with pyraclostrobin (Ravycare<sup>\u00ae<\/sup>). Pyraclostrobin is a carbamate that contains a pyrazole ring. Carbamates are known inhibitors of cholinesterases and the carbamate rivastigmine is already in use for the treatment of Alzheimer\u2019s disease. We tested the type and potency of anticholinesterase activity of mefentrifluconazole and pyraclostrobin. Mefentrifluconazole reversibly inhibited human AChE and BChE with a seven-fold higher potency toward AChE (<em>K<\/em><sub>i<\/sub>\u00a0= 101 \u00b1 19 \u03bcM). Pyraclostrobin (50 \u03bcM) inhibited AChE and BChE progressively with rate constants of (t<sub>1\/2<\/sub>\u00a0= 2.1 min;\u00a0<em>k<\/em><sub>i<\/sub>\u00a0= 6.6 \u00d7 10<sup>3<\/sup>\u00a0M<sup>\u22121<\/sup>\u00a0min<sup>\u22121<\/sup>) and (t<sub>1\/2<\/sub>\u00a0= 1.5 min;\u00a0<em>k<\/em><sub>i<\/sub>\u00a0= 9.2 \u00d7 10<sup>3<\/sup>\u00a0M<sup>\u22121<\/sup>\u00a0min<sup>\u22121<\/sup>), respectively. A molecular docking study indicated key interactions between the tested fungicides and residues of the lipophilic active site of AChE and BChE. Additionally, the physicochemical properties of the tested fungicides were compared to values for CNS-active drugs to estimate the blood\u2013brain barrier permeability. Our results can be applied in the design of new molecules with a lesser impact on humans and the environment.<\/p>\n\n\n\n<p>Rad je dostupan na sljede\u0107oj <a href=\"https:\/\/www.mdpi.com\/1422-0067\/25\/12\/6310\" data-type=\"link\" data-id=\"https:\/\/www.mdpi.com\/1422-0067\/25\/12\/6310\" target=\"_blank\" rel=\"noreferrer noopener\">poveznici<\/a>.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Autori:\u00a0Dora Koli\u0107, Goran \u0160inko Sa\u017eetak radaTriazoles are compounds with various biological activities, including fungicidal action. They became popular through cholinesterase studies after the successful synthesis of the dual binding femtomolar triazole inhibitor of acetylcholinesterase (AChE, EC 3.1.1.7) by Sharpless et al. via\u00a0in situ\u00a0click chemistry. Here, we evaluate the anticholinesterase effect of the first isopropanol triazole &hellip;<br \/><a href=\"https:\/\/projekti.imi.hr\/biomoltox\/2024\/06\/07\/evaluation-of-anticholinesterase-activity-of-the-fungicides-mefentrifluconazole-and-pyraclostrobin\/\" class=\"more-link pen_button pen_element_default pen_icon_arrow_double\">Continue reading <span class=\"screen-reader-text\">Evaluation of Anticholinesterase Activity of the Fungicides Mefentrifluconazole and Pyraclostrobin<\/span><\/a><\/p>\n","protected":false},"author":12,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[13],"tags":[],"class_list":["post-484","post","type-post","status-publish","format-standard","hentry","category-pub-hr"],"acf":[],"_links":{"self":[{"href":"https:\/\/projekti.imi.hr\/biomoltox\/wp-json\/wp\/v2\/posts\/484","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/projekti.imi.hr\/biomoltox\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/projekti.imi.hr\/biomoltox\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/projekti.imi.hr\/biomoltox\/wp-json\/wp\/v2\/users\/12"}],"replies":[{"embeddable":true,"href":"https:\/\/projekti.imi.hr\/biomoltox\/wp-json\/wp\/v2\/comments?post=484"}],"version-history":[{"count":1,"href":"https:\/\/projekti.imi.hr\/biomoltox\/wp-json\/wp\/v2\/posts\/484\/revisions"}],"predecessor-version":[{"id":485,"href":"https:\/\/projekti.imi.hr\/biomoltox\/wp-json\/wp\/v2\/posts\/484\/revisions\/485"}],"wp:attachment":[{"href":"https:\/\/projekti.imi.hr\/biomoltox\/wp-json\/wp\/v2\/media?parent=484"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/projekti.imi.hr\/biomoltox\/wp-json\/wp\/v2\/categories?post=484"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/projekti.imi.hr\/biomoltox\/wp-json\/wp\/v2\/tags?post=484"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}