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 

机构地区：[1]Instituto de Biotecnología,Facultad de Ingeniería,Universidad Nacional de San Juan,CONICET-CCT San Juan,Av.Libertador General San Martín1109(O),5400 San Juan,Argentina [2]Facultad de Química,Bioquímica y Farmacia-IMIBIO-SL(CONICET),Universidad Nacional de San Luis,Chacabuco 915,5700 San Luis,Argentina [3]Laboratorio de Cultivo Celular,Facultad de Ciencias de la Salud,Universidad de Talca,Casilla 747,3460000 Talca,Chile [4]ICYTAC,CONICET and Universidad Nacional de Córdoba,Facultad de Ciencias Químicas,Departamento,Química Orgánica,Ciudad Universitaria,Bv.Juan Filloy s/n,5000 Córdoba,Argentina [5]INFIQC,CONICET and Universidad Nacional de Córdoba,Facultad de Ciencias Químicas,Departamento Química Orgánica,Ciudad Universitaria,Haya de La Torre S/N,5000 Córdoba,Argentina [6]Laboratorio de Química de Productos Naturales,Instituto de Química de Recursos Naturales,Universidad de Talca,Casilla 747,3460000 Talca,Chile

出　　处：《Natural Products and Bioprospecting》2022年第1期107-120,共14页应用天然产物（英文）

摘　　要：Triadimefon(TDM)and cyproconazole(CPZ)are two triazoles widely used as fungicides.Several azoles were synthe-sised starting from commercial TDM and CPZ.The compounds were evaluated against phytopathogenic filamentous fungi,including Aspergillus fumigatus(AF),A.niger(AN),A.ustus(AU),A.japonicus(AJ),A.terreus(AT),Fusarium oxyspo-rum and Botrytis cinerea isolated from grapevine in the province of San Juan,Argentina.Three 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 fungi.Cytotoxicity was assessed using human lung fibroblasts MRC5.Derivative 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 CPZ.The derivatives investigated could be considered broad-spectrum but with some selectivity towards imperfect fungi.

关 键 词：AZOLES Antifungal cytotoxicity Conformational and electronic analysis 

分 类 号：Q5[生物学—生物化学]