Sulfated phenolic compounds from Limonium caspium: Isolation, structural elucidation, and biological evaluation.

Three new compounds, (2S,3S)-5-methyldihydromyricetin (1), (2S,3S)-5-methyldihydromyricetin-3'-O-sulfate (2) and β-d-glucopyranoside, 3-methyl, but-3-en-1-yl 4-O-α-l-rhamnopyranosyl (3) have been isolated from the Limonium caspium, together with dihydromyricetin (4), dihydromyricetin-3'-O-sulfate (5), myricetin-3'-O-sulfate (6), 5-methylmyricetin (7), myricetin (8), myricetin-3-O-β-glucoside (9), as well as phloridzin (10), and tyramine (11). Compounds 5 and 6 were isolated for the first time as acids. This is the first report of all these compounds from this plant. Their structures were established by extensive NMR studies ((1)H NMR, (13)C NMR, DEPT, (1)H-(1)H COSY, HSQC, HMBC) as well as HRESIMS. All isolated compounds were evaluated for their antibacterial, antifungal, antimalarial and antileishmanial activities. Compounds 7, 8 and 9 exhibited good antifungal activity against Candida glabrata with IC50 values of 6.79, 15.37 and 8.53μg/mL, respectively. Compound 8 displayed significant antimalarial activity against resistant and sensitive strains of Plasmodium falciparum with IC50 values of 1.82 and 1.51μg/mL, respectively. Compounds 1, 4, 6, 8 and 9 showed excellent activity against Trypanosoma brucei with IC50 values of 6.93, 9.65, 8.52, 7.67 and 6.31μg/mL, respectively. To date, this is the first report on the phytochemical and biological activity of secondary metabolites from L. caspium.