Design Synthesis and Evaluation of Triarylethylene Analogs as Anti Breast Cancer Agents

Abstract

The breast cancer is the prominent cause of mortality among women and few men. Every 19 seconds, someone is diagnosed with the breast cancer. Thousands of people are dying every year because of this deadly disease. Therefore, the synthesis of new improved anti-breast cancer agents with high potency, low toxicity and specific targets of action is felt highly desirable. newlineThe chapter I of the thesis contains the introduction on anti-breast cancer and the available therapies. It also entails the detailed analysis of estrogen receptors (ERs), their mechanism of actions, Selective Estrogen Receptors Modulators (SERMs) and up to date literature on the synthesis and anti-breast cancer profiles of all known SERMs. The literature survey clearly reveals the following: newlineand#10625; All known triarylethylene analogs as anti-breast cancer agents suffer from varying degrees of disadvantages. newlineand#10625; Over stimulation ofestrogencan be deleterious in some tissues, while remaining a boon in others. newlineand#10625; The triarylethylene moiety is the basic backbone of all SERMs that mimics the action of estrogens by selectively blocking the estrogen to attach to ERs.1 newlineand#10625; Ospemifene (Osp), recently FDA approved SERM, has the most promising pharmacological profile close to an ideal SERM.2 newlineand#10625; Chloro group in Osp reduces the anti-estrogenic activity.3 newlineand#10625; Till date, there is no report on the synthesis and anti-breast cancer evaluation of triarylethylenes having polar amino/amido and thioamido groups and shorter phenoxy alkyl chain in place of longer hydroxyethyl and dimethylaminoethyl chains. newlineKeeping these observations in view, a number of analogs (1-14) of Osp, recently approved by FDA for the treatment of dyspareunia, have been synthesized (Schemes I and II) and evaluated as anti-breast cancer agents against MCF-7 (ER-positive) and MDA-MB-231 (ER-negative) human breast cancer cell lines.The results of these investigations are contained in Chapter II of the thesis. newline newline newline newline