Antimicrobial Acylphloroglucinol Meroterpenoids and Acylphloroglucinols from Dryopteris crassirhizoma

Abstract

Ten novel meroterpenoids, dryoptins/11''-epi-dryoptins A~E (1~10) with an unprecedented skeleton consisting of dimeric or trimeric acylphloroglucinols and dehydrotheonelline, two undescribed acylphloroglucinol-nerolidol meroterpenoids (11~12), and ten known acylphloroglucinol derivatives (13~22), were isolated from D. crassirhizoma. The novel structures including absolute configurations were established by comprehensive spectroscopic analyses and quantum chemical electronic circular dichroism (ECD) calculations. A biosynthetic pathway of 1~10 was assumed. The trimeric acylphloroglucinol meroterpenoids 7/8 showed significant antifungal activity against standard Candida albicans with MIC50 value of 1.61 μg/mL [fluconazole (FLC): 3.41 μg/mL], and when combined with FLC, the principal components 20 and 21 exhibited strong antifungal activities against FLC-resistant C. albicans with MIC50 values of 8.39 and 7.16 μg/mL (FLC: >100 μg/mL), respectively. Moreover, compounds 2, 5/6, 18, 19, and 21 exhibited inhibitory effects against several pathogenic fungi and bacteria, with MIC50 values of 6.25~50 μg/mL.