Research Project
9750775
Abstract. Drug resistance can be a major problem in cancer therapy. The effective treatment of resistant cancer cells can be further complicated by deficiencies that inhibit the body?s own anticancer immune response. Naturally occurring chromanones can inspire the development of drugs to better target cancer resistant cancers as they can directly destroy cancer cells while simultaneously boosting the body?s own immune response. Despite their promising activity, there is a critical barrier obstructing biological studies of chromanone-based bioactive molecules. Specifically, there are limited synthetic strategies available to access these desirable targets for biological testing. As a means to overcome this barrier, the long-term goal of our research programs is to develop chemical technologies to synthesize chromanone-based therapeutic agents for biological studies. Themes directing our investigations include: (i) developing catalytic tools to enable unique, enantioselective heterocycle synthesis; (ii) streamlining access to heterocyclic bioactive targets; and (iii) exploring the biological activities of naturally-occurring chromanones and their synthetic derivatives in the context of drug discovery. This research plan is based on the central hypothesis that silanediol-catalysis is a unique chemical technology enabling access to chromanones, and related structures, that are otherwise difficult to access. The rationale for the proposed research is that the successful development of modular and efficient routes toward chromanone-based natural products, and their derivatives, will enable biological studies of these promising medicinal agents. This approach is innovative because it uses silanediol anion-binding technology to affect pharmaceutically-attractive methodologies that are inaccessible with conventional catalysts. This contribution will be significant as it will support the development of new therapeutic agents able to fight resistant cell cancer lines through unique, dual, synergistic modes of action.
