title: Synthesis and antitumor activity of aromatic camptothecin esters.
abstract: Twenty-eight new aromatic esters of camptothecins 2-29 were prepared in yields of 5 to 96% by straight acylation of camptothecin (1a) and 9-nitrocamptothecin (1b) with various aromatic acids as acylating agents. All of these esters were tested against 14 different human cancer cell lines. The antitumor activity of these compounds was related to the nature of the substituting groups of their side aromatic chains. In general, esters with strong electron-withdrawing groups on their side aromatic chains were active; esters with halogen-substituted side aromatic chains were slightly active; and esters without any substituting groups on their side aromatic chains were practically inactive. The IC50 studies showed that the majority of these esters were not as potent as their parental compounds 1a and 1b; whereas, the potencies of esters 6 and 25 were exceptionally high, much higher than the commercial camptothecin analogues and comparable to (or slightly more potent than) their parental compounds.
authors: The Christus Stehlin Foundation for Cancer Research, Houston, TX 77003, USA. zcao@stehlin.org
authors: Zhisong
authors: Z
authors: Cao
authors: John
authors: J
authors: Mendoza
authors: Albert
authors: A
authors: Dejesus
authors: Dana
authors: D
authors: Vardeman
authors: Beppino
authors: B
authors: Giovanella
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004951:Esterification; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002166:Camptothecin