Plant antitumor agents. 23. Synthesis and antileukemic activity of camptothecin analogs

Eight optically active and nine racemic ring A modified analogues of 20(S)-camptothecin were prepared and evaluated for antitumor activity in the L-1210 leukemia system. The ring A mono- and disubstituted analogues displayed a wide variance in activity and potency. It was found that monosubstitution...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1986-11, Vol.29 (11), p.2358-2363
Main Authors: Wani, Mansukh C, Nicholas, Allan W, Wall, Monroe E
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents, Phytogenic - chemical synthesis
Antineoplastic Agents, Phytogenic - pharmacology
Camptothecin - analogs & derivatives
Camptothecin - pharmacology
Leukemia L1210 - drug therapy
Solubility
Structure-Activity Relationship
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Summary:Eight optically active and nine racemic ring A modified analogues of 20(S)-camptothecin were prepared and evaluated for antitumor activity in the L-1210 leukemia system. The ring A mono- and disubstituted analogues displayed a wide variance in activity and potency. It was found that monosubstitution by NH2 or OH at positions 9, 10, or 11 yielded compounds with activity much higher than the parent compound, camptothecin, whereas substitution at position 12 greatly reduced activity. In general, disubstitution in ring A greatly reduced antileukemic activity. Replacement of ring A by heterocyclic rings (thiophene or pyridine) leads to analogues with only moderate activity.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00161a035