Research Projects

Cancer has become a major global public health crisis, with rising incidence and mortality rates. Despite advancements in cancer biology and treatment, the number of new cancer diagnoses continues to increase, with nearly 20 million new cases in 2022 and 9.7 million deaths worldwide. Current treatments face challenges such as drug resistance and severe side effects, leading to a growing interest in natural products as potential sources for new anticancer drugs. Many existing cancer treatments, such as paclitaxel and vincristine, are derived from natural sources, demonstrating their potential in oncology. Natural compounds, with their diverse and targeted properties, offer hope for overcoming the limitations of conventional therapies and improving cancer treatment. We propose a highly efficient and scalable route for the total synthesis of Mallotumides (A−C), which are potent cytotoxic cycloheptapeptides effective against a diverse range of cancer cell lines. These natural products have shown remarkable inhibition of cell viability, with IC₅₀ values between 0.60 nM and 4.02 nM. Establishing a successful synthetic pathway will provide access to Mallotumides in substantial quantities, facilitating further research into their biological properties. Additionally, these studies could contribute to a structure-activity relationship (SAR) analysis of Mallotumide derivatives, aiding in the discovery of effective anti-cancer agents. We have proposed simple and efficient synthetic strategy to access Mallotumides and their analogs from easily accessible starting materials. The proposed synthetic route is notable for its flexibility, allowing for the rapid generation of multiple analogues of the natural products. Following the synthesis of Mallotumides and their analogs, these compounds will be evaluated for their anti-cancer properties. By investigating a variety of analogs with different structural modifications, this research seeks to identify the key components of the pharmacophore—be they particular functional groups, stereochemical arrangements, or conformational characteristics—that are crucial for sustaining or enhancing biological activity. The ultimate objective is to discover a lead compound or a class of compounds with improved pharmacological profiles, potentially leading to the development of more effective and viable drug candidates.