NMR studies on novel antitumor drug candidates, deoxoartemisinin and carboxypropyldeoxoartemisinin.
Artemisinin and its derivatives, which have been known as antimalarial drugs, have also demonstrated their cytotoxicity against tumor cells. It has been proposed that antitumor activity depends on the lipophilicity of functional group on artemisinin derivatives. Solution structures of two artemisinin derivatives as antitumor drug candidates, deoxoartemisinin and carboxypropyldeoxoartemisinin, were determined by NMR spectroscopy to elucidate structure-activity relationship. According to biological assay, antitumor efficiencies are not dependent upon lipophilicity. Instead, these compounds demonstrated their distinctive structural features of boat/chair conformation and capability to interact with receptors, as they have different efficiencies on antitumor activity. Especially, carboxypropyl moiety or carbonyl moiety in artemisinin derivatives influences the conformation and stability of ring structure. Although the detailed mechanism of antitumor activity by artemisinin derivatives has not been addressed, we suggest that antitumor activity is not determined only with lipophilicity and that artemisinin derivatives have specific target proteins in each type of cancer.
Department of Biochemistry, College of Science, Yonsei University, Seoul, Korea.
C H
CH
Lee
H
H
Hong
J
J
Shin
M
M
Jung
I
I
Shin
J
J
Yoon
W
W
Lee
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D037621:Artemisinins; D002247:Carbon Isotopes; D002522:Chlorocebus aethiops; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014407:Tumor Cells, Cultured; D014709:Vero Cells
D000970:Antineoplastic Agents; D037621:Artemisinins; D002247:Carbon Isotopes; D012717:Sesquiterpenes; C412376:carboxypropyldeoxoartemisinine; C063801:deoxoartemisinin