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

Abstract

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 (SN2), 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.

The anti‐breast cancer therapeutic potential of 1,2,3‐triazole‐containing hybrids

“…1,2,3-Triazole-tetrazole hybrids 17 (IC 50 : 19.76-200 µM, MTT assay) showed weak to moderate antiproliferative activity against MCF-7 breast cancer cells, and the SAR elucidated that halogen atom at R 2 position could improve the activity to some extent. [37] Among them, hybrids 17a,b (IC 50 : 19.76 and 22.84 µM) exhibited the highest activity against MCF-7 breast cancer cells and could act as lead compounds for further structural modifications. 1,2,3-Triazole-isoxazole hybrid 18 (Figure 5; IC 50 : 7.24 µM, MTT assay) was comparable to doxorubicin (IC 50 : 4.62 µM) against MCF-7 breast cancer cells, and the SAR illustrated that incorporation of methyl group into para-position of phenyl ring at N-2 position of 1,2,3-triazole moiety decreased the activity.…”

“…1,2,3‐Triazole‐tetrazole hybrids 17 (IC 50 : 19.76–200 µM, MTT assay) showed weak to moderate antiproliferative activity against MCF‐7 breast cancer cells, and the SAR elucidated that halogen atom at R 2 position could improve the activity to some extent. [ 37 ] Among them, hybrids 17a,b (IC 50 : 19.76 and 22.84 µM) exhibited the highest activity against MCF‐7 breast cancer cells and could act as lead compounds for further structural modifications.…”

Aldehyde Phenylamino-Pyrimidine as Key Precursor for the Synthesis of Imatinib Analogs and In Silico Studies of Their Intermediates

“…In the first step, an amino-PAP 4 diazotization/addition reaction was performed, resulting in an 80% yield of azide-PAP 7. The second step involved a copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) between propargylic alcohol 8 and azide-PAP 7, using reaction conditions recently described by our research group [18], yielding the primary alcohol triazole-PAP 9 with a 75% yield. Finally, oxidation of the primary alcohol with IBX produced the aldehyde triazole-PAP 3 with a 40% yield.…”

Late‐stage functionalization of Vouacapane derivatives from Caesalpinia platyloba by a Groebke−Blackburn−Bienaymé reaction

“…[ 16–18 ] To our delight, the 6 β ‐acetoxyvouacapane 9 or their derivatives have not been used as starting reagents in multicomponent reactions. Therefore, since there are only two reports describing the use of natural products or their derivatives in the GBB reaction, and in continuation with our research program on the synthesis of biologically relevant compounds via I‐MCRs, [ 19–22 ] we describe here a late‐stage functionalization of a small series of fused Vouacapane‐azoles 11a‐f via the GBB reaction (Scheme 1C).…”