Abstract:

To develope an efficiently structural modification strategy for transforming antibacterial fluoroquinolone into antitumor agent, novel N-arylidene arylidene rhodanine levofloxacin amide derivatives(6a-6n) were synthesized via amide modification with functionalized arylidene rhodanine scaffold as the bioisostere of the C-3 carboxylic group. The in vitro antitumor assay indicated that the title compounds exhibited more significant potency against three test cancer cell lines than levofloxacin, but with lower cytotoxicity against the normal cells than doxorubicin as a comparison. The SAR(structure-activity relationship) reveals that the increase in the bulky or electron-donating substituents bearing phenyl ring obviously reduces the antitumor activity. Conversely, compounds with electron-withdrawing nitro- or fluorophenyl or heteroaromatic rings such as furan or pyridine ring display comparable activity to doxorubicin. Thus, an amide group modified by arylidene rhodanine scaffold as an isostere of the C-3 carboxylic acid group appears to an alternative route for further design of antitumor fluoroquinolone.

Key words: fluoroquinolone, amide, rhodanine, α,β-unsaturated ketone, bioisostere, antitumor activity