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

Maroua Bourkhis, Dymytrii Listunov, Hafida Gaspard, Etienne Joly, Raoudha Abderrahim, Valérie Maraval, Yves Génisson, Remi Chauvin


A recently proposed "ethynylogation" pharmacochemical 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⋮ and ⋮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)2C(OH)–C≡CR and its bis-lipidic counterpart HC≡C–C(OH)(C≡CR)2 were synthesized in 4 steps and with 33 % and 23 % overall yield, respectively. Their antitumor cytotoxicity has been evaluated towards HCT116 cells: while the latter TAC is totally inactive, the former DAC-ethynylogous TAC still exhibits a significant toxicity with an IC50 of 10 µM.


alkyne; antitumor agent; ethynylogation; lipid; pharmacophore design; trialkynylcarbinol

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