Synthesis, Antifungal Activity, Cytotoxicity and QSAR Study of Camphor Derivatives

Control of fungal phytopathogens affecting crops and woodlands is an important goal in environmental management and the maintenance of food security. This work describes the synthesis of 37 camphor derivatives, of which 27 were new compounds. Their antifungal effects on six fungi were evaluated in vitro. Compounds 3a, 4a and 5k showed strong antifungal activity against Trametes versicolor, with EC(50) values of 0.43, 6.80 and 4.86 mg/L, respectively, which were better than that of tricyclazole (EC(50) 118.20 mg/L) and close to or better than that of carbendazim (EC(50) 1.20 mg/L). The most potent compound, 3a, exhibited broad-spectrum antifungal activity towards six fungi with EC(50) values within the range of 0.43–40.18 mg/L. Scanning electron microscopy demonstrated that compounds 3a, 4a and 5k gave irregular growth and shriveling of the mycelia. In vitro cytotoxicity evaluation revealed that the tested camphor derivatives had mild or no cytotoxicity for LO(2) and HEK293T cell lines. Quantitative structure−activity relationship (QSAR) analysis revealed that the number of F atoms, relative molecular weight, the atomic orbital electronic population and total charge on the positively charged surfaces of the molecules of camphor derivatives have effects on antifungal activity. The present study may provide a theoretical basis for a high-value use of camphor and could be helpful for the development of novel potential antifungals.