Targeting aromatase to restrain oestrogen production and developing efficacious interventions against ER-positive cancer

Being the most frequently diagnosed disease, breast Cancer is mainly classified as ER+ cancers due to the detection of Estrogen Receptor (ER) expression. Irrespetive of the successes achieved in the treatment of ER+ cancers by the use of selective Estrogen receptor Modulator (SERM) drugs like tamoxifen, resistance to the drug is a major clinical obstacle. Working on alternative treatment approaches, here, on the basis of mode of action of aromatase for the conversion of androstenedione to oestrogen, a series of compounds was developed. Results of all the experiments performed with these compounds led to the identification of three highly potent compounds 5d, 5e and 7d with their IC₅₀ 61.0, 83.0 and 54.0 nM for aromatase. Indicating their effectiveness in the treatment of ER+ cancers, appreciable tumor growth inhibitory activities of these compounds were observed against breast Cancer cell lines. Further, the physico-chemical experiments including plasma protein binding, HSA binding, kinetic studies, solubility, ADME properties and molecular modelling studies supported the drug like features of the compounds.

Anti-Aromatase activity; Indole; McMurry coupling; Molecular modelling; Pharmacokinetics; Serum albumin; Triphenylethylene derivatives.