Abstract

Cancer is the top cause of mortality and a significant impediment to extending life expectancy. In 2020, there were 19.3 million new cancer cases and nearly 10.0 million cancer deaths worldwide. Despite advancements in cancer prevention, early identification, surgical management, and adjuvant radio- and chemotherapy, curing cancer patients remains an elusive objective, with a strong need to develop more effective therapies¹.In medicinal chemistry, the sulphonamide moiety has become very prominent and a number of sulphonamide derivatives have been discovered with a variety of biological activities, including antibacterial, antifungal, antioxidant, anti-inflammatory, anti-cancer, and anti-diabetic properties. Some of the anti-cancer targets of sulphonamide derivatives that have recently progressed as potential anticancer therapies include aromatase, carbonic anhydrase (CA), anti-apoptotic B-cell lymphoma-2 (Bcl-2) proteins, topoisomerase, and phosphatidylinositol 3-kinase (PI3K) ². One of the hallmarks of cancer is the ability to evade apoptosis, and it plays a key role in cancer cell resistance to chemotherapies. Overexpression of anti-apoptotic Bcl-2 proteins leads to sequestration of pro-apoptotic Bcl-2 proteins, which is linked to the genesis and progression of many human malignancies. As a result, anti-apoptotic Bcl-2 proteins have been proposed as potential cancer therapeutic targets³. In this regard, we synthesized a new chemical library of sulfonamide derivative and investigated its anticancer activity and possible mode of action. The research discovered a hit capable of causing apoptotic cell death. We are currently characterizing the hit compound to find out its mechanism of action by focusing on distinct sulphonamide targets including Bcl-2 and AKT. We expect that with further optimization, the molecule will be a good lead for the subsequent phases of therapeutic development. In the second part we have explored the gold complexes for cancer therapeutics. Gold (I) complexes are prospective chemotherapeutic agents with exceptional anti-proliferative efficacy against particular human cancer cell lines that are resistant to traditional platinum-based chemotherapeutics⁴. Several Gold complexes with very potent (lower nanomolar range) antiproliferative activity have been identified. Further research is needed to determine their mechanism of action including their effect on apoptosis, cell cycle arrest and DNA damage response.

Evaluation Committee

Dr. Ghayoor Abbas (Supervisor)

Dr. Amir Faisal (Thesis Committee Member)

Dr. Rahman Shah Zaib Saleem (Thesis Committee Member)