Synthesis and evaluation of coumate analogues as estrogen receptor inhibitors for breast cancer therapy

Abstract

A sulphatase inhibitor 667 COUMATE is in clinical trials for estrogen-positive breast cancer therapy for postmenopausal women, while there are a number of similar sulphatase inbitors are under development. Schiff's bases are versatile pharmacophores in which the N atom involves in hydrogen bonding with active cell centers interfering in normal cell biology. A library of novel coumate analogues with Schiff bases were designed, and structural based drug design was performed with human estrogen receptor (PDB ID: 2IOG) (Already reported). Based on the in-silico outcomes, seven coumate-schiff bases were synthesized. The compounds were obtained in good yield. The novelty had been ascertained by sci finder software. The synthesized molecules were consistent with their assigned spectra such as IR, Mass and NMR spectral data which confirmed their formation. The cytotoxicity study was performed by MTT assay for all the synthesized compounds. Most of the compounds have good IC₅₀ values (below 100 µg/ml).Two of the synthesized compounds COU-2 and COU-5 have shown good IC₅₀ values such as 19µg/ml and 39µg/ml, respectively. They suppressed the proliferation of estrogen receptor overexpressed MCF-7 cells.