A One-Pot Six-Component Reaction for the Synthesis of 1,5-Disubstituted Tetrazol-1,2,3-Triazole Hybrids and Their Cytotoxic Activity against the MCF-7 Cell Line

A high-order multicomponent reaction involving a six-component reaction to obtain the novel linked 1,5-disubstituted tetrazole-1,2,3-triazole hybrids in low to moderate yield is described. This one-pot reaction is carried out under a cascade process consisting of three sequential reactions: Ugi-azide, bimolecular nucleophilic substitution (S(N)2), and copper-catalyzed alkyne-azide reaction (CuAAC), with high atom and step-economy due the formation of six new bonds (one C-C, four C-N, and one N-N). Thus, the protocol developed offers operational simplicity, mild reaction conditions, and structural diversity. Finally, to evaluate the antitumoral potential of the synthetized molecules, a proliferation study was performed in the breast cancer (BC) derived cell line MCF-7. The hybrid compounds showed several degrees of cell proliferation inhibition with a remarkable effect in those compounds with cyclohexane and halogens in their structures. These compounds represent potential drug candidates for breast cancer treatment. However, additionally assays are needed to elucidate their complete effect over the cellular hallmarks of cancer.

Automated summary

This study presents a high-order multicomponent reaction to obtain novel linked 1,5-disubstituted tetrazole-1,2,3-triazole hybrids in low to moderate yield. The cascade process involves Ugi-azide, bimolecular nucleophilic substitution (S(N)2), and copper-catalyzed alkyne-azide reaction (CuAAC), forming six new bonds. The synthesized hybrid compounds show potential as drug candidates for breast cancer treatment, especially those with cyclohexane and halogens in their structures, although further assays are needed to fully understand their effects on cancer cell hallmarks.