Cycloart-24-ene-26-ol-3-one, a New Cycloartane Isolated from Leaves of Aglaia exima Triggers Tumour Necrosis Factor-Receptor 1-Mediated Caspase-Dependent Apoptosis in Colon Cancer Cell Line.

Plants in the Meliaceae family are known to possess interesting biological activities, such as antimalaral, antihypertensive and antitumour activities. Previously, our group reported the plant-derived compound cycloart-24-ene-26-ol-3-one isolated from the hexane extracts of Aglaia exima leaves, which shows cytotoxicity towards various cancer cell lines, in particular, colon cancer cell lines. In this report, we further demonstrate that cycloart-24-ene-26-ol-3-one, from here forth known as cycloartane, reduces the viability of the colon cancer cell lines HT-29 and CaCO-2 in a dose- and time-dependent manner. Further elucidation of the compound's mechanism showed that it binds to tumour necrosis factor-receptor 1 (TNF-R1) leading to the initiation of caspase-8 and, through the activation of Bid, in the activation of caspase-9. This activity causes a reduction in mitochondrial membrane potential (MMP) and the release of cytochrome-C. The activation of caspase-8 and -9 both act to commit the cancer cells to apoptosis through downstream caspase-3/7 activation, PARP cleavage and the lack of NFkB translocation into the nucleus. A molecular docking study showed that the cycloartane binds to the receptor through a hydrophobic interaction with cysteine-96 and hydrogen bonds with lysine-75 and -132. The results show that further development of the cycloartane as an anti-cancer drug is worthwhile.

Triterpenes and steroids from the leaves of Aglaia exima (Meliaceae).

A study on the leaves of Aglaia exima led to the isolation of one new and seven known compounds: six triterpenoids and two steroids. Their structures were elucidated and analyzed mainly by using spectroscopic methods; 1D and 2D NMR, mass spectrometry, UV spectrometry and X-ray. All the triterpenoids and steroids were measured in vitro for their cytotoxic activities against eight cancer cell lines; lung (A549), prostate (DU-145), skin (SK-MEL-5), pancreatic (BxPC-3), liver (Hep G2), colon (HT-29), breast (MCF-7) and (MDA-MB-231). The new cycloartane triterpenoid, 24(E)-cycloart-24-ene-26-ol-3-one 1, showed potent cytotoxic activity against colon (HT-29) cancer cell line (IC(50) 11.5µM).

Cabraleahy-droxy-lactone from the leaves of Aglaia exima.

Cabraleahy-droxy-lactone, C(27)H(44)O(3), isolated from the leaves of Aglaia exima, has three six-membered rings fused together that adopt chair conformations. Its two five-membered rings are enveloped shaped. The hy-droxy group is in an axial position. It is a hydrogen-bond donor to the carbonyl O atom of an adjacent mol-ecule; the O-H⋯O inter-actions lead to the formation of a helical chain that runs along the b axis. There are two independent mol-ecules in the asymmetric unit.

Cyclo-art-24-ene-3ß,26-diol from the leaves of Aglaia exima.

Cyclo-art-24-ene-3ß,26-diol, C(30)H(50)O(2), isolated from the leaves of Aglaia exima, has three six-membered rings fused together that adopt chair conformations. There are two independent mol-ecules in the asymmetric unit. O-H⋯O hydrogen bond inter-actions between the hydroxyl groups in the 3ß and 26 positions lead to the formation of a layer structure parallel to (10).