Ethynylogation approach in antitumor lipid pharmacochemistry: from dialkynyl-carbinols to trialkynyl-carbinols

A recently proposed "ethynylogation" pharmacomodulation approach, first envisaged in the series of anticancer lipidic dialkynylcarbinols (DACs) H-C C-CH(OH)-C C-R at the levels of the H-C 3 vertical dots and 3 vertical dots C-R bonds for R = n-C12H25, is completed here at the level of the (HO) C-H bond. The so-devised mono-lipidic trialkynylcarbinol (TAC) target (HC C)(2)C(OH)-C CR and its bis-lipidic counterpart HC C-C(OH)(C CR)(2) were synthesized in 4 steps with 33 % and 23 % overall yield, respectively. Their antitumor cytotoxicity has been evaluated towards HCT116 cells: while the latter doubly lipidic TAC is totally inactive (IC50 > 120 mu M), the former DAC-ethynylogous TAC still exhibits a significant toxicity with an IC50 of 40 mu M.