Synthesis and biological activities of fluorinated 10-hydroxycamptothecin and SN38

• Fluorinated 10-hydroxycamptothecin and SN 38 were prepared by four steps.
• Fluorinated camptothecin derivative MF-6 showed potent antiproliferative activities.
• We have obtained potent camptothecin derivatives by fluorine substitution strategy.
• C-21 carbonyl group of camptothecin is unnecessary to antitumor activity.

It is an important strategy for fluorine substitution in drug design because of its small size and high electronegativity. Fluorinated 10-hydroxycamptothecin and SN 38 were prepared and screened for antiproliferative activities. Among them, fluorinated compound MF-6 showed higher antiproliferative activities against A549, HCT116 and MDA-MB-435 cancer cells than unfluorinated compound. The result of Topoisomerase I activity also confirmed that the C-21 carbonyl group of camptothecin structure is unnecessary to antitumor activity.

Fluorinated 10-hydroxycamptothecin and SN 38 were prepared and screened for antiproliferative activities. Compound MF-6 showed higher antiproliferative activities against A549, HCT116 and MDA-MB-435 cancer cells than that of the parent compound SN 38.Figure optionsDownload as PowerPoint slide