Synthesis and biological activity of desmethoxy analogues of coruscanone A

Desmethoxy analogues of coruscanone A were prepared via Ti( iPrO) 4 mediated condensation of cyclopentenedione with aldehydes. Antifungal activity of 2-benzylidenecyclopent-4-ene-1,3-dione was comparable to those of coruscanone A and fluconazole, and was superior to the drug standard against several non-albicans Candida species. Experiments on antiproliferative activity indicated lower cytotoxicity compared to the natural product. A series of simple desmethoxy analogues of coruscanone A was prepared via a novel version of Ti( iPrO) 4-mediated Knoevenagel condensation of cyclopentenedione with substituted benzaldehydes and cinnamic aldehydes, and the compounds were evaluated for antifungal activity and cytotoxicity. The most potent 2-benzylidenecyclopent-4-ene-1,3-dione possessed antifungal effect comparable to coruscanone A and a somewhat broader spectrum of activity against Candida species. The compound was also superior to fluconazole against several non-albicans Candida sp. Evaluation of the ability of the compound to influence cell proliferation using two different assays showed that 2-benzylidenecyclopent-4-ene-1,3-dione has lower cytotoxicity compared to the natural product.