Exploring the molecular diversity of phenolic acids and polyphenols to advance the knowledge for the development of new biologically-active molecules

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The proposed research program involves exploring the diversity of polyphenols and phenolic acids by the synthesis of new analogs through the adaptation of organic synthesis and medicinal chemistry methodologies while including molecular modeling. Based on the results obtained in recent years, the use by the applicant of the molecular diversity of phenolic acids and polyphenols will allow the development of new molecules. The determination of associated structure-activity relationships will help advance knowledge for the development of new biologically active molecules. Whether by inhibiting the biosynthesis of their products or through their direct inhibition, the effects of novel phenolic acids or polyphenols-based analogs on lipoxygenases and cyclooxygenases, key enzymes involved in the inflammatory cascade, will be investigated. Phenolic acids and polyphenols, which are widely distributed natural compounds, will be used as building blocks to construct specific and efficient molecules. Due to the link between inflammation and cancer, anticancer activity tests will be carried out in collaboration with the applicant's network of collaborators. Similarly, in vivo tests with the applicant's collaborators of select compounds in animal models of disease such as inflammatory arthritis are projected. Elucidating the structure-activity relationships of the newly developed analogs will expand knowledge for the development of selective and efficient bioactive molecules while limiting adverse effects. Over the next five years, 4 graduate and 6 undergraduate students will receive high quality training in the art of organic and medicinal chemistry, and other research-related skills. In addition to imparting intensive highly qualified personnel training, this program will expand the number of approaches available for the synthesis of biologically-relevant analogs of phenolic acids and polyphenols where molecular diversity is in great demand. The medicinal chemistry community working on the development of new phenolic acids or polyphenols-based analogs and the general population will benefit from the outcomes of the proposed research program.