The objectives of our research program in lamellarins are:
1) to utilize our developed method to synthesize a number of unnatural lamellarins to probe the structure of binding site in the binding pocket of lamellarins with DNA-topoisomerase I ternary complex,
2) to prepare more potent anticancer drug candidates of the lamellarin skeleton based on the information from the binding site (objective 1),
3) to prepare lamellarin analogs which possess other desirable pharmacological properties e.g. better aqueous solubility and lower toxicity against normal cells, and
4) to simplify lamellarin structure to contain only the moieties necessary for the biological activities.
