Isolation and Structural Elucidation of New Biologically Active Secondary Metabolites from Asphodelus microcarpus

Bioassay-guided fractionation of the ethanolic extract of Aspodelus microcarpus Salzm. et Vivi (Asphodelaceae) resulted in the isolation of a novel metabolite, 3,10-dimethoxy-5-methyl-1H-1,4 epoxybenzo[h]isochromen (1), three new compounds: asphodelin-10'-oxanthrone-10'-β-D-arabinopyranoside (2), chrysalodin-10'-oxanthrone-10'-β-D-glucopyranoside (3) and 1,6-dimethoxy-3-methyl-2-naphthoic acid (4) as well as eight known compounds: asphodelin (5), chrysophanol (6), 8-methoxy chrysophanol (7), 2-acetyl,1,8-dimethoxy,3-methyl naphthalene (8), 10-(chrysophanol-7′-yl)-10-hydroxychrysophanol-9-anthrone (9), aloesaponol III -8-methyl ether (10), ramosin (11) and eastivin (12) [1 – 4]. Identification of the compounds was carried out by using 1D and 2D NMR as well as HRESIMS experiments. Compounds (6) and (8) were isolated for the first time from this species. Compounds (6) and (7) showed moderate to weak antileishmanial activity with IC₅₀ values of 14.3 and 35.1 µg/mL, respectively. Compound (7) exhibited moderate antifungal activity against Cryptococcus neoformans with an IC₅₀ value of 15.0 µg/mL, while compound (9) and compound (12) showed good to potent activity against methicillin resistant Staphylococcus aureus (MRSA) with IC₅₀ values of 9.43 µg/mL and 1.4 µg/mL respectively. Compounds (10) and (11) displayed good activity against S. aureus with IC₅₀ values of 7.3 and 8.5 µg/mL, respectively. Compounds (9) and compound (11) exhibited a moderate to potent cytotoxic activity against leukemia K562 cell lines respectively. Compound (12) showed antimalarial activities against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum with IC₅₀ values in the range of 0.84 – 0.72 µg/mL without showing any cytotoxicity to the mammalian cells. Acknowledgments: Thanks go to the National Center for Natural Products Research, also thanks to Dr. Bharthi Avula for HRMS, Dr. Melissa Jacob, Dr. Babu Tekwani and Dr. Jiangtao Gao for antimicrobial, antileishmanial and antileukmic assays. References: [1] Mohammed AI, Ragab EA (2008) Egypt J Biomed Sci, 27: 52 – 61. [2] Dagne E, Steglich W (1984) Phytochemistry, 23: 1729 – 1731. [3] Todorova G, Lazorova I, et al. (2010) Chemistry of Natural Compounds, 46: 322 – 323. [4] Lanzetta R, Parrilli M (1990) Tetrahedron, 46: 1287 – 1294.