Cytotoxicity of endemic Haplophyllum megalanthum Bornm. and its newly isolated alkaloids and lignans

In this study, two previously unreported lignans [4′-O-demetylsuchilactone-8′-ol (1), 7-O-(3-methyl-2,3-dihydroxy-butyl)isodaurinol] (2), four new alkaloids (haplomegalanthine (3), megalantin (4), megalanthamide (5), glycoisohaplopine (6) and thirty-five known compounds (7–41) were isolated from Haplophyllum megalanthum Bornm. (Rutaceae). Pinoresinol (23), epipinoresinol (24), indole-3-carbaldehyde (29), N-[2-(4-hydroxyphenyl)ethyl]-3-methylbut-2-enamide (34), 7,8-dimethoxyfuroquinoline-4-one (35), cis-khellactone (36), 4,4′-dihydroxy-3,3′,9-trimethoxy-9,9′-epoxylignan (37), ulopterol (39) and trans-decursidinol (40) were identified for the first time in the genus Haplophyllum. Also, 4′-O-demethylsuchilactone (16) and N-(4-hydroxyphenethyl)benzamide (32) were found for the first time within the family Rutaceae. Structures of the compounds were elucidated by the use of HRMS, UHPLC-MS and 1D/2D NMR analyses. Furthermore, cytotoxic activity of the crude extract and previously unreported compounds (1–3, 5, 6) on colon cancer cell line HT29 were tested by the MTT method. IC₅₀ values were determined for these five compounds and the crude extract as 18.48 ± 0.94 μg/ml, 52.62 ± 7.27 μg/ml, 23.15 ± 6.70 μg/ml, 21.45 ± 2.48 μg/ml, 5.06 ± 0.19 μg/ml and 2.82 ± 0.012 μg/ml, respectively. The present report is the first detailed phytochemical investigation of the title plant pointing out that it comprises a rich source of diverse chemical constituents including new compounds with promising cytotoxic activity.