Laboratory of Drug Discovery, Center for Research and Education on Drug Discovery

Research

2. Development of physiologically active natural products into drug discovery

Though natural products are good drug discovery leads, it is difficult to make themselves medicines directly. That is to say, it is required to advance them into simple and drug-like molecules by conducting molecular design on them. Simplifying the structures of natural products with maintaining its activity and function makes it possible not only to reduce of time consuming and producing cost but also to enhance activity and improve ADMET by post-chemical modification. By examining structure-activity relationship and conducting logical design of drugs based on computational chemistry, we will advance simplification of natural products, identify the target molecules by using probe of active compounds, elucidate binding mode accurately, and head to elucidate mechanism of action and logical design of drugs.

Besides the research of structure-activity relationship of natural products, we have proceeded the research below. For example, by way of structure-activity relationship of caprazamycin group and logical drug design by computational chemistry, we have found out isoxazolidine derivatives whose molecular weight was reduced by 2/3 and has anti-MRSA and VRE activity as effective as natural products. Furthermore, by using Domino-type intramolecular 1,3-dipolar cycloaddition, we achieved more effective and comprehensive synthesis. We also conducted simplification research of staurosporin, which have anticancer activity, and we found a strong and selective protein kinase inhibitor.

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