Molecular Genetic and Cytotoxic Evaluation of Novel Synthesized Hybrid Steroid Derivatives as Chemotherapeutic Anti-Breast Cancer Agents

Abstract

Hybrid anti-cancer agents, which combine two biologically active compounds in one such as steroidal heterocyclic derivatives attain both hormone and cytotoxic effects on cancer cells. The aim of the present study is to synthesize and evaluate new potential hybrid chemotherapeutic anti-breast cancer agents. Several pyridazino-, pyrimido-, quinazolo-, oxirano- and thiazolo steroid derivatives were synthesized using 3-hydroxy-5a-androstan-17-one (epi-androsterone) 1 as starting steroid. The structure of the novel steroid derivatives was confirmed using the analytical and spectral data. The most structurally promising of the novel synthesized hybrid steroids, compounds 8, 12, 17, 20, 22c, 24c, 30a and 30b, were investigated individually as anti­ breast cancer agents against the human breast cancer cells (MCF-7) using SRB assay. The tested compounds 17, 20, 22c and 8 showed promising broad spectrum cytotoxic activity in vitro after 48 hour incubation. Compound 17 (IC50 = 2.5f1M) exhibited more inhibition effect of MCF-7 growth than Dox (IC50 = 4.5f1M) after 48 h incubation time. The results of the present study showed that all the tested hybrid steroid derivatives showed significant decrease with various intensities in gene expression of breast cancer related genes (VEGF, CYP19, hAP-2y and hAP- 2a). Compounds 17, 20 and 22c were the more effective in this respect.