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 IC(50) values in the 0.2-2.2 μM range, while IC(50) 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.
Université de Toulouse, UPS, Laboratoire de Synthèse et Physicochimie de Molécules d'Intérêt Biologique (LSPCMIB), Groupe de RMN Biomédicale, 118 route de Narbonne, 31062 Toulouse Cedex 9, France.
Alexander
A
Korolyov
Sandra
S
Dorbes
Joëlle
J
Azéma
Brigitte
B
Guidetti
Mathieu
M
Danel
Delphine
D
Lamoral-Theys
Thierry
T
Gras
Jacques
J
Dubois
Robert
R
Kiss
Robert
R
Martino
Myriam
M
Malet-Martino
D000577:Amides; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001555:Benzene Derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004952:Esters; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D064704:Levofloxacin; D015242:Ofloxacin
D000577:Amides; D000970:Antineoplastic Agents; D001555:Benzene Derivatives; D002264:Carboxylic Acids; D004952:Esters; D064704:Levofloxacin; D015242:Ofloxacin