Research Projects

Despite the recent advances in therapies, cancer is still the second leading cause of death in the Unites States and a major cause of morbidity and mortality worldwide. Natural products have been an important source for drug development over the decades as more than 70% of the currently available drugs are either directly from natural sources or semi-synthetic analogues of natural products or molecules developed inspired by natural products. Out of 136 chemotherapeutic drugs used against cancer, 83% are from natural sources or modified compounds of natural products. Due to the invasiveness, toxicity and ineffectiveness of current therapeutic approaches, there has been intense interest in using natural and dietary compounds for prevention and treatment of cancer. Owing to it’s anticancer properties and robust apoptotic nature; capsaicin has gained a lot of interest in cancer drug discovery. In the speedily evolving era, Natural product-based discovery of combinational compounds/multi-targeted therapies have been revealed promising and trending pattern. Hybrid conjugation of bioactive ligands is a new strategy in drug discovery based on the combination of bioactive fragments to design new hybrid molecules under one construct with enhanced affinity and efficacy. Multi-target compounds may be achieved by using the concept of hybridization in the drug development. The purpose of this concept is to find therapeutic agents that are able to demonstrate more promising pharmacokinetic and pharmacodynamic parameters. The following one/two/three-point modifications has envisioned to afford some new hybrid capsaicinoids: 1. Structural modification of Capsaicin 2. Modulation of liphophilic chain (tail). 3. Diaryl ethers/amine conjugates of capsaicinoids with modified liphophilic chain (Head & Tail). 4. PROTAC conjugated capsaicinoids 5. Three-dimensional modification of capsaicin at head, neck, tail with bioactive heterocycles. 6. Anti-proliferative activity of new hybrid conjugates (hybrid capsaicinoids) against NCI-panel of 60 Cancer cell lines. 7. Evaluation of In vitro VEGF inhibitory potentials of novel capsaicinoids. 8. Generation of secondary lead molecules and development of SAR As part of our ongoing work on the development of natural product inspired bioactive ligands; a novel capsaicinoid has been developed with excellent in vitro anti-proliferative activity with GI50 values ranging between ranging between 0.3-3.62 µM against all the NCI panel of 60 human cancer cell lines (data obtained from National Cancer Institute-USA). This class of compounds were found to inhibit VEGF markers markedly. Inspired by these preliminary results and keeping in view of the biological importance of capsaicin/capsaicinoids as anticancer agents we aim to develop some novel class of capsaicinoids as VEGF inhibitors.