Synthesis and biological evaluation of novel tamoxifen-1,2,4-triazole conjugates

A new class of compounds, structurally related to the breast cancer drug tamoxifen, was designed and synthesized. The McMurry coupling reaction was used as the key synthetic step in the preparation of these analogs, and the structural assignments were made on the basis of $$^{1}\hbox {H}$$ NMR, $$^{13}\hbox {C}$$ NMR, and HRMS studies. The absolute stereochemistry of E and Z isomers was unambiguously confirmed by a single-crystal X-ray diffraction analysis. Water was found to be an inexpensive nontoxic and effective medium for the C–N bond formation. Utilizing this protocol, various tamoxifen derivatives were synthesized in good yields. Environmental acceptability, low cost, and high yields are the important features of this protocol. These compounds were evaluated for their antiproliferative activity on five human tumor cell lines. Compound 4p ( $$\mathrm{GI}_{50} = 0.23\,\upmu \hbox {M}$$ ) showed improved antiproliferative activity against breast cancer cell line (MDA-MB-231) compared to tamoxifen ( $$\mathrm{GI}_{50} = 0.24 \,\upmu \hbox {M}$$ ), while the compound 4o ( $$\mathrm{GI}_{50} = 0.12\,\upmu \mathrm{M}$$ ) exhibited similar activity against SiHa compared to the reference drug, tamoxifen ( $$\mathrm{GI}_{50} = 0.12\,\upmu \mathrm{M}$$ ). In addition, these analogs were investigated for their antibacterial activity against six bacterial strains. Preliminary results indicate that some of the newly synthesized title compounds exhibited promising antibacterial activity compared with the standard drug, vancomycin. A new class of compounds were designed rationally by the replacement of a ethyl group in tamoxifen with a methylene (1H-1,2,4-triazole) group. The absolute stereochemistry of E and Z isomers were unambiguously confirmed by a single-crystal X-ray diffraction analysis. The title compounds were evaluated for their antiproliferative and antibacterial activities.