Antitumor activity of novel deoxoartemisinin monomers, dimers, and trimer.
The first primary amines 9 and bromoalkyl analogues 7 of deoxoartemisinin with nonacetal functionality at C-12 are prepared as versatile intermediates for the synthesis of various derivatives. Eight C-12 nonacetal type dimers and one trimer of deoxoartemisinin were prepared using novel chemistry. Dimers, particularly 12a, 18a,b, and trimer 17, were especially potent and selective at inhibiting the growth of certain human cancer cell lines and were comparable to that of clinically used anticancer drugs. The linker with one amide- or one sulfur-centered two ethylene groups of the dimers is essential for high anticancer activity. Trimer 17 shows very potent activity against most of the human cancer cell lines tested.
Jung
Mankil
M
Department of Chemistry, Yonsei University, Seoul 120-749, Korea. mkjung@alchemy.yonsei.ac.kr
Lee
Sangmin
S
Ham
Jungyeob
J
Lee
Kyunghoon
K
Kim
Hanjo
H
Kim
Soo Kie
SK
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D037621:Artemisinins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D011108:Polymers; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D037621:Artemisinins; D011108:Polymers; D012717:Sesquiterpenes; C063801:deoxoartemisinin