Cytotoxic Lanostanoids from <i>Poria cocos</i>

Abstract

Six new and 16 known lanostanoids were isolated from the sclerotia of Poria cocos . The structures of the new isolates were elucidated to be 16α-hydroxy-3-oxo-24-methyllanosta-5,7,9(11),24(31)-tetraen-21-oic acid ( 1 ), 3β,16α,29-trihydroxy-24-methyllanosta-7,9(11),24(31)-trien-21-oic acid ( 2 ), 3β,16α,30-trihydroxy-24-methyllanosta-7,9(11),24(31)-trien-21-oic acid ( 3 ), 3β-acetoxy-16α,24β-dihydroxylanosta-7,9(11),25-trien-21-oic acid ( 4 ), 3β,16α-dihydroxy-7-oxo-24-methyllanosta-8,24(31)-dien-21-oic acid ( 5 ), and 3α,16α-dihydroxy-7-oxo-24-methyllanosta-8,24(31)-dien-21-oic acid ( 6 ), based on extensive spectroscopic analyses. The absolute configuration of 4 was determined using Mosher’s method. The antiproliferative activity of the isolated compounds (except 3 and 4 ) was evaluated against four leukemic cell lines (Molt 4, CCRF-CEM, HL 60, and K562). Dehydropachymic acid ( 9 ), dehydroeburicoic acid ( 12 ), pachymic acid ( 14 ), and lanosta-7,9(11),24-trien-21-oic acid ( 20 ) exhibited an antiproliferative effect on the CCRF-CEM cancer cell line with IC 50 values of 2.7, 6.3, 4.9, and 13.1 μM, respectively. Both dehydropachymic acid ( 9 ) and dehydroeburicoic acid ( 12 ) showed antiproliferative effects against Molt 4 (IC 50 13.8 and 14.3 μM) and HL 60 (IC 50 7.3 and 6.0 μM) leukemic cell lines. Primary computational analysis using a chemical global positioning system for natural products (ChemGPS-NP) on the active lanostanoids from P. cocos suggested that targets other than topoisomerases may be involved in the antiproliferative activity.