Executive Summary : | Panduratins A-F, a group of structurally diverse cyclohexenyl chalcones, have been used as folk medicines in Indonesia, Malaysia, and Thailand for various ailments. They exhibit anticancer, antioxidant, anti-inflammatory, antibacterial, and anti-biofilm activities. Panduratin A inhibits cell proliferation and induces apoptosis in colon cancer cells, decreases the incidence of aberrant crypt foci in rats with colon cancer, and results in cell growth inhibition and induction of apoptosis in A549 non-small cell lung cancer cells. The therapeutic benefits of panduratins B-F and analogous compounds remain relatively unexplored due to their low natural abundance and lack of synthesis. This study aims to propose an enantionselective total synthesis of panduratin A-F and its analogues, providing an important route to highly bioactive molecules. The researchers will develop a route for accessing appropriate chalcone dienophiles from phloroglucinol, conduct an asymmetric Diels-Alder reaction with different chiral ligands and catalysts, and convert the Diels-Alder adducts to different natural products. The newly synthesized compounds will be used in vitro cytotoxicity evaluation against breast and lung cancer cell lines, as these are the most common cancers in females and males, respectively. The probable anticancer mechanism will be elucidated using compounds with potent IC50 values, and molecular modeling will be performed to rationalize the anti-cancer activity, sARs, and binding mode within selected targets. The proposal stems from the global interest in the synthesis and biological evaluation of these compounds and the continued interest in the synthesis of bioactive natural products. |