New ursane triterpenoids from Ficus pandurata and their binding affinity for human cannabinoid and opioid receptors

다국어 초록 (Multilingual Abstract)

Phytochemical investigation of Ficus pandurataHance (Moraceae) fruits has led to the isolation of two newtriterpenoids, ficupanduratin A [1b-hydroxy-3b-acetoxy-11a-methoxy-urs-12-ene] (11) and ficupanduratin B [21ahydroxy-3b-acetoxy-11a-methoxy-urs-12-ene] (17), alongwith 20 known compounds: a-amyrin acetate (1), a-amyrin(2), 3b-acetoxy-20-taraxasten-22-one (3), 3b-acetoxy-11amethoxy-olean-12-ene (4), 3b-acetoxy-11a-methoxy-12-ursene (5), 11-oxo-a-amyrin acetate (6), 11-oxo-b-amyrinacetate (7), palmitic acid (8), stigmast-4,22-diene-3,6-dione(9), stigmast-4-ene-3,6-dione (10), stigmasterol (12), b-sitosterol(13), stigmast-22-ene-3,6-dione (14), stigmastane-3,6-dione (15), 3b,21b-dihydroxy-11a-methoxy-olean-12-ene (16), 3b-hydroxy-11a-methoxyurs-12-ene (18), 6-hydroxystigmast-4,22-diene-3-one (19), 6-hydroxystigmast-4-ene-3-one (20), 11a,21a-dihydroxy-3b-acetoxy-urs-12-ene(21), and b-sitosterol-3-O-b-D-glucopyranoside (22). Compound21 is reported for the first time from a natural source.
The structures of the 20 compounds were elucidated on thebasis of IR, 1D (1H and 13C), 2D (1H–1H COSY, HSQC,HMBC and NOESY) NMR and MS spectroscopic data, inaddition to comparison with literature data. The isolatedcompounds were evaluated for their anti-microbial, antimalarial,anti-leishmanial, and cytotoxic activities. In addition,their radioligand displacement affinity on opioid andcannabinoid receptors was assessed. Compounds 4, 11, and15 exhibited good affinity towards the CB2 receptor, withdisplacement values of 69.7, 62.5 and 86.5 %, respectively.
Furthermore, the binding mode of the active compounds inthe active site of the CB2 cannabinoid receptors was investigatedthrough molecular modelling.

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