Novel lipophilic 7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid derivatives as potential antitumor agents: Improved synthesis and in vitro evaluation

A convenient route for the synthesis of some acyloxymethyl esters and carboxamides of levofloxacin (LV) with modulated lipophilicity is described. The synthesized compounds were evaluated in vitro for their growth inhibitory effect in five human cancer cell lines. The most efficient LV derivatives (ester 2e and amide 4d) displayed IC50 values in the 0.2–2.2 μM range, while IC50 values for parent LV ranged between 70 and 622 μM depending on the cell line. The esters displayed no in vivo toxicity up to 80 mg/kg when administered intraperitoneally. This study thus shows that LV analogs displayed antitumor efficacy, at least in vitro, a feature that appeared to be independent from the lipophilicity of the grafted substituent.

Acyloxymethyl esters and carboxamides derived from levofloxacin were prepared and investigated in vitro for antiproliferative activity against five human cancer cell lines. Nine derivatives displayed mean IC50 values in the micromolar range.Figure optionsDownload as PowerPoint slide