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

Maroua Bourkhis (1, 2) , Dymytrii Listunov (3, 4) , Hafida Gaspard (1) , Etienne Joly (5) , Raoudha Abderrahim (2) , Valérie Maraval (3) , Yves Génisson (1) , Rémi Chauvin (3, 4)

1 SPCMIB - Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique
2 LaboratoiredePhysiquedesMatériauxLamellairesetNanomatériauxHybrides(LPMLNMH), Département de physique
3 LCC - Laboratoire de chimie de coordination
4 UT3 - Université Toulouse III - Paul Sabatier
5 IPBS - Institut de pharmacologie et de biologie structurale

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.

Mots clés: Alkyne; Antitumor agent; Ethynylogation; Lipid; Pharmacophore design; Trialkynylcarbinol

Domaines: Chimie de coordination

Maroua Bourkhis, Dymytrii Listunov, Hafida Gaspard, Etienne Joly, Raoudha Abderrahim, et al.. Ethynylogation approach in antitumor lipid pharmacochemistry: from dialkynyl-carbinols to trialkynyl-carbinols. French-Ukrainian Journal of Chemistry, 2017, 5 (1), pp.24-34. ⟨10.17721/fujcV5I1P24-34⟩. ⟨hal-01939396⟩