NMR studies on novel antitumor drug candidates, deoxoartemisinin and carboxypropyldeoxoartemisinin

Artemisinin and its derivatives, which have been known as antimalarial drug s, have also demonstrated their cytotoxicity against tumor cells. It has be en proposed that antitumor activity depends on the lipophilicity of functio nal group on artemisinin derivatives. Solution structures of two artemisini n derivatives as antitumor drug candidates, deoxoartemisinin and carboxypro pyldeoxoartemisinin, were determined by NMR spectroscopy to elucidate struc ture-activity relationship. According to biological assay, antitumor effici encies are not dependent upon lipophilicity. Instead, these compounds demon strated their distinctive structural features of boat/chair conformation an d capability to interact with receptors, as they have different efficiencie s on antitumor activity. Especially, carboxypropyl moiety or carbonyl moiet y in artemisinin derivatives influences the conformation and stability of r ing structure. Although the detailed mechanism of antitumor activity by art emisinin derivatives has not been addressed, me suggest that antitumor acti vity is not determined only with lipophilicity and that artemisinin derivat ives have specific target proteins in each type of cancer. (C) 2000 Academi c Press.