Institution: Interamerican University Bayamon Campus

Email: cospina@bayamon.inter.edu

In the area of cancer, approximately 65% of the total drugs approved by the FDA from 1981 to 2019 are natural products or their derivatives possessing distinct families of chemical compounds. These data indicate that research in natural products continues to be a field of interest for the discovery of new drugs to treat cancer. However, less than 15% of plants have been assessed of their bioactive potential, emphasizing a critical need for the discovery of novel bioactive compounds from unexplored plant species. In our ongoing efforts to discover new compounds with anticancer activity, we reported the isolation and elucidation of the quassinoid simalikalactone D (SKD) which showed potent in vitro cytotoxicity effect at nanomolar concentrations on breast cancer cell lines. However, SKD showed a similar effect on normal human mammary epithelial cells. Therefore, future studies will include determining the usefulness of SKD in adjuvant chemotherapy by delivering SKD using a targeted delivery system to selectively affect cancer cells. The proposed research will address a gap in knowledge on the development of novel safety quassinoids formulations with potential uses in cancer treatment. The overall goal is the discovery, characterization, and development of SKD and derivatives as anticancer agents. The central hypothesis is that pure quassinoids isolated from Simarouba species and formulated in a drug delivery system will affect selectively cancer cells and reduce potential toxicity effects. The rationale comes from the literature, and from our own study that quassinoids are important leads that could be developed against cancer disease and drug delivery systems using formulations of nanoparticles that have demonstrated effectiveness in current anticancer treatments. The specific aims of this project are to evaluate the in vitro antitumor activity of a novel SKD-trastuzumab nanoliposomal formulation in HER2 overexpressing breast cancer cell lines and to demonstrate the anticancer potential of new quassinoids isolated from plants of Simaroubacea family. The proposed aims will impact the area of drug discovery, drug delivery and cancer research from medicinal plants by adding new knowledge on the role of natural products in liposomal nanomedicine for breast cancer therapy.