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

摘要

A series of 1H-1,2,3 triazole grafted tetrahydro-beta-carboline-chalcone/ferrocenylchalcone conjugates were synthesized andin vitroevaluated 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 were13l(R = 4-F,n= 3), which exhibited an IC(50)value of 10.33 mu M against MCF-7 and was similar to 5 fold more potent than the standard drug Tamoxifen, while13d(R = 2,3,4-trimethoxy,n= 5) exhibited an IC(50)value of 21.99 mu M against the MDA-MB-231 cells, being similar to 3 fold more potent than Tamoxifen. The experimental results were further supported by the molecular docking studies in the ligand binding domain of ER alpha and a greater binding affinity has been attributed to the energetically favourable fit and balance between the hydrophobic and hydrophilic interactions in the ER alpha active site.