Design, synthesis, and anti-proliferative evaluation of 1H-1,2,3-triazole grafted tetrahydro-β-carboline-chalcone/ferrocenylchalcone conjugates in estrogen responsive and triple negative breast cancer cells

Abstract

A series of 1H-1,2,3 triazole grafted tetrahydro-β-carboline-chalcone/ferrocenylchalcone conjugates were synthesized and in vitro evaluated against estrogen responsive (MCF-7) and triple negative (MDA-MB-231) breast cancer cells. Comparative analysis revealed the improvement of selectivity towards the estrogen responsive cells with the inclusion of a ferrocene core. The most potent compounds of the series were 13l (R = 4-F, n = 3), which exhibited an IC₅₀ value of 10.33 μM against MCF-7 and was ∼5 fold more potent than the standard drug Tamoxifen, while 13d (R = 2,3,4-trimethoxy, n = 5) exhibited an IC₅₀ value of 21.99 μM against the MDA-MB-231 cells, being ∼3 fold more potent than Tamoxifen. The experimental results were further supported by the molecular docking studies in the ligand binding domain of ERα and a greater binding affinity has been attributed to the energetically favourable fit and balance between the hydrophobic and hydrophilic interactions in the ERα active site.