Abstract 

According to the World Health Organization (WHO), approximately 180K new cancer cases were reported in Pakistan in 2020, out of which around 14. 5% were breast cancer cases. Among all cancer related deaths, the breast cancer is still the number 1 cause of death in Pakistani women. Most of the breast cancer cases are hormone receptor positive, i.e., the cancer cells have one of the hormone receptors, particularly the estrogen receptor (ER) overexpressed. Therefore, the clinical management of ER+ cases include the use of selective estrogen receptor modulators (SERM) such as tamoxifen, clomiphene, and raloxifene, etc as a successful treatment option. Nevertheless, breast cancer can relapse, or the treatment can often fail due to the development of drug resistance in some patients. Therefore, only a sustained effort in the discovery and development of new therapeutic agents can warrant a sustained fight against the breast cancer.

My MS research is focused on the design and discovery of new anticancer drugs by targeting the over-expressed ERs in breast cancer. As a raloxifene mimic, we intend to synthesize a library of small organic molecules on a benzothiophene scaffold, which would then be tested for the SERM activity in ER-positive breast cancer cells. Recently, a model reaction between 2-mercaptobenzoic acid and phenacyl bromide resulted in the construction of a benzothiophene ring in a single step, which has encouraged us to explore the versatility and scope of this reaction. Thus, starting from 2-mercaptobenzoic acid, a series of benzothiophene derivatives have been synthesized in an expeditious reaction using several substituted phenacyl bromides. Spectroscopic data, including ¹H- and ¹³C NMR, GCMS, and IR, confirmed the formation of the desired product. The synthesized compounds were further tested using breast cancer cell line, indicating their promising anticancer potential. Since benzothiophene is a privileged scaffold for medicinally important compounds, the synthesized library will also be used to test biological activities against other types of carcinomas.

In the future, we will diversify our benzothiophene library to conduct a comprehensive structure-activity relationship study and to extend the benzothiophene scaffold by incorporating additional interesting heterocyclic rings.

Thesis Committee

• Dr. Muhammad Saeed (supervisor)
• Dr. Irshad Hussain (thesis committee member)
• Dr. Basit Yameen (thesis committee member)