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 a MIC 50 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 MIC 50 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 MIC 50 values of 6.25 ~ 50 µg/mL.

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