Cytotoxic Alkylynols of the Sponge : Structure, Synthetic Analogs and SAR Studies.

A series of twenty-three linear and branched chain mono acetylene lipids were isolated from the Caribbean Sea sponge . Seventeen of the compounds, , are new, while six, , were previously characterized from the same sponge. Some of the new acetylene-3-hydroxy alkanes , , , , were tested for selective cytotoxicity in non-small cell lung carcinoma (NSCLC) cells over WI-38 normal diploid lung fibroblasts. Compound , presented clear tumor selective activity while, and , showed selectivity at lower doses and and , were not active towards NSCLC cells at all. The earlier reported selective cytotoxicity of some acetylene-3-hydroxy alkanes ( and ), in NSCLC cells and/or other tumor cell types were also confirmed for , and . To further study the structure activity relationships (SAR) of this group of compounds, we synthesized several derivatives of acetylene-3-hydroxy alkanes, -, -, -, -, -, -, -, -, -, -, -, -, - and -, along with other 3-substituted derivatives, -, -, -, -, - and -, and assessed their cytotoxic activity against NSCLC cells and diploid fibroblasts. SAR studies revealed that the alcohol moiety at position 3 and its absolute configuration both were essential for the tumor cell line selective activity while for its cytotoxic magnitude the alkyl chain length and branching were of less significance.