Antitubercular and Cytotoxic Constituents from Goniothalamus gitingensis

Phytochemical studies on the leaves of the Philippine endemic Annonaceae plant, Goniothalamus gitingensis enabled the isolation and identification of four secondary metabolites corresponding to three styryllactones, isoaltholactone (1), altholactone (2) and goniopypyrone (3), and the alkaloid liriodenine (4). Structure identification was facilitated through various spectroscopic experiments such as NMR ( 1H, 13C, COSY, HSQC, HMBC and NOESY), LR-EIMS, X-ray and through comparison with literature values. Our study accounts the first report of all compounds in this plant species. The extracts together with the isolated compounds (1-4) were tested for antituberculosis activity using MABA and cytotoxic activity using the CellTiter-Blue1 assay. The majority of the samples tested indicated good inhibitory activity against Mycobacterium tuberculosis H 37Rv (MIC up to 16 m g/mL). Liriodenine (4) showed the most excellent antimycobacterial activity (MIC=16 m g/mL) followed by 1 and the 5:4 mixture of 1 and 2. Their cytotoxicity against three human cancer cell lines, human umbilical vein endothelial cell line (HUVEC), human leukemia cell line (K-562) and HeLa cells were also assessed. The crude extract, alkaloid extract, petroleum ether sub-extract and EtOAc sub-extract showed moderate cytotoxicity against the cancer cell-lines. In addition, the results showed that compounds 1, 4 and the mixture of 1 and 2 exhibited highest cytotoxicity against HUVEC, K-562 and HeLa cell lines with GI 50 values up to 4 μg/mL (vs. HUVEC and/or K-562) and CC 50 values up to 25.1 μg/mL (vs. HeLa).