Cytotoxic Activity and Structure-Activity Relationship of Triazole-Containing Bis(Aryl Ether) Macrocycles

ChemMedChem
Eduardo Hernández-VázquezLuis D Miranda

Abstract

Cancer continues to be a worldwide health problem. Certain macrocyclic molecules have become attractive therapeutic alternatives for this disease because of their efficacy and, frequently, their novel mechanisms of action. Herein, we report the synthesis of a series of 20-, 21-, and 22-membered macrocycles containing triazole and bis(aryl ether) moieties. The compounds were prepared by a multicomponent approach from readily available commercial substrates. Notably, some of the compounds displayed interesting cytotoxicity against cancer (PC-3) and breast (MCF-7) cell lines, especially those bearing an aliphatic or a trifluoromethyl substituent on the N-phenyl moiety (IC50 <13 μm). Additionally, some of the compounds were able to induce apoptosis relative to the solvent control; in particular, (Z)-N-cyclohexyl-7-oxo-6-[4-(trifluoromethyl)phenyl]-11 H-3,10-dioxa-6-aza-1(4,1)-triazola-4(1,3),9(1,4)-dibenzenacyclotridecaphane-5-carboxamide (12 f) was the most potent in this regard (22.7 % of apoptosis).

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Citations

Jan 24, 2019·Organic & Biomolecular Chemistry·Alejandra Chávez-RiverosLuis D Miranda
Apr 25, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Odette ConcepciónClaudio A Jiménez
Mar 17, 2021·Bioorganic & Medicinal Chemistry Letters·Eduardo Hernández-VázquezLuis D Miranda
Jun 4, 2019·Chemical Reviews·Ivan V SmolyarValentine G Nenajdenko

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