Abstract 1094 Biological Evaluation of Indolylfuranones as Potential Anti-Cancer Agents

The American Cancer Society estimates that this year there will be approximately over 2 million new cases of cancer and 600,000 cancer-related deaths in 2024.The need for new and innovative anti-cancer drugs is increasingly crucial.One attractive anti-cancer target is tubulin, which is involved in many cellular functions including cell shape, mitosis, migration, and movement of organelles.While anti-tubulin drugs have been used to treat cancer for 70 years, they tend to be complex molecules derived from natural products, suffer from multi-drug resistance, have low solubility, exhibit toxicity issues, and/or the lack of multi-cancer efficacy.These limitations highlight the continued need for the discovery and development of new and novel drugs to enter the pipeline, especially with the significant increase in understanding of tubulin and the mode of action of inhibitors.Using an interdisciplinary approach with undergraduate researchers, we previously developed a furanone-containing small molecule, PY-407-C.The compound demonstrated nanomolar anti-proliferative activity against cancer cells.We subsequently confirmed that it inhibited tubulin polymerization in vitro.We now report on a suite of compounds expanding from PY-407-C.This work has identified new compounds with strong cytotoxicity and important structure-function information.Overall, these studies provide basic research on small molecule inhibitors of cancer.