Sesquiterpene lactones from the extracts of two Balkan endemic Laserpitium species and their cytotoxic activity

Abstract

Chloroform extracts of the underground parts of two Balkan endemic Laserpitium species, Laserpitium zernyi Hayek and Laserpitium ochridanum Micevski, were chemically investigated. Five unknown guaianolides from the class of slovanolides, of which four were additionally 2β-esterified, as well as two lactones, previously identified in other Laserpitium species, were isolated from the L. ochridanum extract. From the L. zernyi extract one slovanolide derivative was isolated for the first time in the genus Laserpitium. In addition, the phenylpropanoid latifolone and six known sesquiterpene lactones, characterised as derivatives of slovanolide and silerolide, were isolated from the extracts of both species. The cytotoxic activities of the total extracts and the isolated compounds were tested using MTT and SRB assays on the two human breast cancer cell lines, MCF 7/6 and MCF 7/AZ. The extracts exerted cytotoxic activities with the IC(50) values ranging 65.21-348.25 μg/mL. The L. ochridanum extract was most potent in the MTT test with IC(50) values of 65.21 and 66.09 μg/mL in the MCF 7/AZ and MCF 7/6 cell lines, respectively. The highest cytotoxic activity exerted 2β,8α-di-angeloyloxy-10β-hydroxy-6αH-guaian-3,(7-11)-dien-12,6-olide, a slovanolide derivative with an additional double bond in lactone ring, on highly invasive MCF 7/6 cell line, with IC(50) value 0.7 μM in both assays tested. Generally, guaianolides with a higher number of ester moieties at the positions 2β, 8α, 10β or 11α exhibited IC(50) values in the micromolar range, while eudesmanolides and guaianolides with a lower number of esters did not induce significant cytotoxicity.