Stability and hydrolysis studies of novel dual acting conjugate drugs with anitcancer activity

Abstract

Tamoxifen is currently a first-line endocrine therapy for the adjuvant treatment of Estrogen Receptor (ER) positive breast cancer. The antiestrogenic properties of this compound are related to its ability to compete for estrogen binding sites in target tissues such as the breast and bone. In this research project carried in the Pharmaceutical Chemistry research laboratory in the School of Pharmacy and Pharmaceutical Sciences, a novel series of estrogen receptor modulators was developed. Some of these compounds prevent estrogen binding to its receptor with a higher potency than Tamoxifen, while also inhibiting the proliferation of a human MCF- 7 breast carcinoma cell line. In this study the physiochemical properties and specific structural requirements of drug-like molecules for optimum estrogen receptor binding are examined. The stability of these ligands which are active at the estrogen receptor are specifically investigated.The study of novel potent drug candidates coupled with the elucidation of the mode of action will advance our understanding of and ability to combat hormone dependent breast cancer. The design, synthesis, biochemistry and stability of dual acting estrogen receptor conjugates are now investigated.