| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1396383 | European Journal of Medicinal Chemistry | 2010 | 7 Pages |
The homocamptothecin (hCPT) represents a new class of topoisomerase inhibitor which combines enhanced plasma stability and strong antitumor activity. Fluorine imparts desirable characteristics to drugs by modulating both the pharmacokinetics and pharmacodynamic properties of a drug. Therefore, in an attempt to improve the antitumor activity of homocamptothecins, seven new 7-trifluoromethylated homocamptothecin derivatives were prepared by proline-catalyzed Friedlander annulation. The antitumor activity in vitro and in vivo on cancer cell lines, and inhibitory properties of topoisomerase I-mediated DNA cleavage of compounds 6c and 8b were evaluated. Several of these trifluoromethylated hCPT derivatives (such as 6a, 6b and 6c) possessed higher in vitro antitumor activity than topotecan (TPT). Especially, the compound 6c showed effective in vivo antitumor activity comparable to that of TPT.
Graphical abstractSeven new 7-trifluoromethylated homocamptothecin derivatives were prepared firstly by proline-catalyzed Friedlander annulation. Several of these fluorinated derivatives possessed higher antitumor activities than Topotecan (TPT).Figure optionsDownload full-size imageDownload as PowerPoint slide
