CHEMICAL CONSTITUENTS AND DERIVATIZATION OF MELODORINOL FROM THE ROOTS OF Melodorum fruticosum Lour.

Abstract

The phytochemical investigation of the CH2Cl2 and MeOH crude extracts from the roots of M. fruticosum led to the isolation of four triterpenoids, β-sitosterol (1), stigmasterol (2), polycarpol (3) and lanosta-7,9(11),24-trien-3β,21-diol (12), four heptenes, acetylmelodorinol (4), melodorinol (7), (4Z)-6-benzoyloxy-7-hydroxy-2,4-heptadien-4-olide (8) and (4Z)-6,7-dihydroxy-2,4-heptadien-4-olide (13), six flavonoids, chamanetin (5), chrysin (6), pinocembrin (9), isochamanetin (10), dichamanetin (11) and catechin (14), and one terpenoid glycoside, ampelopsisionoside (15). Their structures were elucidated on basis of spectroscopic data as well as comparison with the previous literature data. All isolated compounds were evaluated on cytotoxicity against KB, HeLa, MCF-7 and HepG-2 cells. Chamanetin (5) showed good selectivity on cytotoxicity against only KB cell with IC50 value of 0.86 µg/mL, while acetylmelodorinol (4) showed the highest cytotoxicity against both KB and HeLa with IC50 values of 0.66 and 0.66 µg/mL. The terpenoids revealed moderate to inactive cytotoxicity against all cell lines. Based on their cytotoxicity results, heptenes presented the lowest cytotoxic values against all of four cell lines. Melodorinol (7) was selected for further derivertization to yield six new (7a-7d and 7f-7g) and one known (7e) melodorinol derivatives. All of derivatives were tested against four cell lines. The analogue propanoylmelodorinol (7b) exhibited the most active against KB, HeLa, MCF-7 and HepG-2 with IC50 values of 0.64, 0.75, 0.78 and 3.57 µg/mL, respectively. Preliminary structure activity relationships analysis of functional groups on cytotoxicity effects were benzoyl, lactone ring, and hydrophobic ester groups in heptene core scaffolds.