Synthesis and antitumor activity of fluoroquinolone C-3 s-triazole Schiff-base carboxylic acid derivatives from pefloxacin (X) / 中国药科大学学报

ABSTRACT

To explore a new strategy for further optimization to the C-3 bioisteric heterocyclic ring of fluoroquinolones,twelve novel fluoroquinolone C-3 s-triazole Schiff-base carboxylic acid derivatives(7a-71) were designed and synthesized with both functionalized sulfanylacetic acid and Schiff-base moieties as the modified side-chain for the C-3 bioisosteric s-triazole ring of pefloxacin(1).The structures were characterized by elemental analysis and spectral data,and the in vitro anti-tumor activity of the title compounds against SMMC-7721,L1210 and HL60 cell lines was evaluated.The preliminary pharmacological results demonstrated that the title compounds possessed more significantly anti-proliferative activity than either the parent 1 or the corresponding amine intermediates(6).In particular,the title compound bearing a fluorine atom (7j) and compound bearing a nitro group attached to benzene ring (71) were comparable to the control doxorubicin against SMMC-7721 cells with an IC50 value of micro-molar concentration,respectively.It suggests that s-triazole ring modified with functional side-chain moieties instead of the C-3 carboxylic group is favorable to the improvement of antitumor activity.