Synthesis and antitumor activity of A-ring modified hexacyclic analogues of camptothecin.
OBJECTIVE
To improve the biological activity of A-ring modified analogues of camptothecin.


METHODS
A-ring modified camptothecins were synthesized from 10-hydroxycamptothecin or 7-ethyl-10-hydroxycamptothecin (SN-38) in three or four steps. Their cytotoxicity was evaluated using MTY assay, and their in vivo antitumnor activity against mouse liver cancer H22 was tested. Results Five hexacyclic camptothecins (6a, 6b, 6c, 7a and 7b) are target compounds, and ten camptothecin derivatives are new compounds.


CONCLUSIONS
The modification of a 1,4-oxazine-2-one ring fused with positions 9 and 10 of A-ring will reduce the antitumor activity of camptothecins.
Li
Di-zao
DZ
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Vedical College, Beijing 100050, China.
Wang
Cun-ying
CY
Pan
Xian-dao
XD
Liu
Hong-yan
HY
Fu
Zhao-di
ZD
Wu
Song
S
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D009368:Neoplasm Transplantation; D011083:Polycyclic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology
D000970:Antineoplastic Agents; D011083:Polycyclic Compounds; D000077146:Irinotecan; C028098:10-hydroxycamptothecin; D002166:Camptothecin