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

HERRERA CANO, NATIVIDAD; ANDUJAR, SEBASTIAN A.; THEODULOZ, CRISTINA; WUNDERLIN, DANIEL A.; SANTIAGO, ANA N.; SCHMEDA-HIRSCHMANN, GUILLERMO; ENRIZ, RICARDO D.; FERESIN, GABRIELA E.

Natural Products and Bioprospecting

Springer

Lugar: Ney York; Año: 2022 vol. 12

2192-2195

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 flamentousfungi, including Aspergillus fumigatus (AF), A. niger (AN), A. ustus (AU), A. japonicus (AJ), A. terreus (AT), Fusarium oxysporum and Botrytis cinerea isolated from grapevine in the province of San Juan, Argentina. Three of the synthesisedcompounds (1-(Biphenyl-4-yloxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)butan-2-one, 1; 2-(Biphenyl-4-yl)-3-cyclopropyl1-(1H-1,2,4-triazol-1-yl)butan-2-ol, 3; 3-Cyclopropyl-2-(4?-fuorobiphenyl-4-yl)-1-(1H-1,2,4-triazol1-yl)butan-2-ol, 4)presented remarkable in vitro fungicidal properties, with better efects than TDM and CPZ on some of the target fungi.Cytotoxicity was assessed using human lung fbroblasts MRC5. Derivative 1, with IC50 values of 389.4 µM, was lesstoxic towards MRC-5 human lung fbroblasts than commercial TDM (248.5 µM) and CPZ (267.4 µM). Docking analy‑sis and molecular dynamics simulations suggest that the compounds present the same interaction in the bindingpocket of the CYP51B enzyme and with the same amino acids as CPZ. The derivatives investigated could be consid‑ered broad-spectrum but with some selectivity towards imperfect fungi