Arylated analogues of cypronazole: fungicidal effect and activity on human fibroblasts. Docking analysis and molecular dynamics simulations

作     者：Natividad Herrera Cano Sebastian A.Andujar Cristina Theoduloz Daniel A.Wunderlin Ana N.Santiago Guillermo Schmeda-Hirschmann Ricardo D.Enriz Gabriela E.Feresin 

作者机构：Instituto de BiotecnologíaFacultad de IngenieríaUniversidad Nacional de San JuanCONICET-CCT San JuanAv.Libertador General San Martín1109(O)5400 San JuanArgentina Facultad de QuímicaBioquímica y Farmacia-IMIBIO-SL(CONICET)Universidad Nacional de San LuisChacabuco 9155700 San LuisArgentina Laboratorio de Cultivo CelularFacultad de Ciencias de la SaludUniversidad de TalcaCasilla 7473460000 TalcaChile ICYTACCONICET and Universidad Nacional de CórdobaFacultad de Ciencias QuímicasDepartamentoQuímica OrgánicaCiudad UniversitariaBv.Juan Filloy s/n5000 CórdobaArgentina INFIQCCONICET and Universidad Nacional de CórdobaFacultad de Ciencias QuímicasDepartamento Química OrgánicaCiudad UniversitariaHaya de La Torre S/N5000 CórdobaArgentina Laboratorio de Química de Productos NaturalesInstituto de Química de Recursos NaturalesUniversidad de TalcaCasilla 7473460000 TalcaChile 

出 版 物：《Natural Products and Bioprospecting》 (应用天然产物（英文）)

年 卷 期：2022年第12卷第1期

页      面：107-120页

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 

基　　金：supported by the Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET) Secretaria de Ciencia y Tecnologia (SECYT-UNC) CICITCA UNSJ IMIBIO-UNSL and Agencia Nacional de Promocion Cientifica y Tecnologica (ANPCyT) 

主　　题：Azoles Antifungal cytotoxicity Conformational and electronic analysis 

摘      要：Triadimefon(TDM)and cyproconazole(CPZ)are two triazoles widely used as *** azoles were synthe-sised starting from commercial TDM and *** compounds were evaluated against phytopathogenic filamentous fungi,including Aspergillus fumigatus(AF),***(AN),***(AU),***(AJ),***(AT),Fusarium oxyspo-rum and Botrytis cinerea isolated from grapevine in the province of San Juan,*** of the synthesised compounds(1-(Biphenyl-4-yloxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)butan-2-one,1;2-(Biphenyl-4-yl)-3-cyclopropyl-1-(1H-1,2,4-triazol-1-yl)butan-2-ol,3;3-Cyclopropyl-2-(4’-fluorobiphenyl-4-yl)-1-(1H-1,2,4-triazol1-yl)butan-2-ol,4)presented remarkable in vitro fungicidal properties,with better effects than TDM and CPZ on some of the target *** was assessed using human lung fibroblasts *** 1,with IC50 values of 389.4μM,was less toxic towards MRC-5 human lung fibroblasts than commercial TDM(248.5μM)and CPZ(267.4μM).Docking analysis and molecular dynamics simulations suggest that the compounds present the same interaction in the binding pocket of the CYP51B enzyme and with the same amino acids as *** derivatives investigated could be considered broad-spectrum but with some selectivity towards imperfect fungi.