title: Synthesis and antitumor activity of A-ring modified hexacyclic analogues of camptothecin.
abstract: 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.
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Vedical College, Beijing 100050, China.
authors.forename: Di-zao
authors.initials: DZ
authors.lastname: Li
authors.forename: Cun-ying
authors.initials: CY
authors.lastname: Wang
authors.forename: Xian-dao
authors.initials: XD
authors.lastname: Pan
authors.forename: Hong-yan
authors.initials: HY
authors.lastname: Liu
authors.forename: Zhao-di
authors.initials: ZD
authors.lastname: Fu
authors.forename: Song
authors.initials: S
authors.lastname: Wu
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D011083:Polycyclic Compounds; D000077146:Irinotecan; C028098:10-hydroxycamptothecin; D002166:Camptothecin