The Assessment of cytotoxicity, apoptosis inducing activity and molecular docking of a new ciprofloxacin derivative in human leukemic cells

Abstract

The fluoroquinolone class of antibiotics includes derivatives of the drug ciprofloxacin. These substances have recently been advocated for the treatment of cancer. In the current study, we examined the cytotoxicity and apoptosis-inducing potential of a novel synthetic ciprofloxacin derivative in the human myeloid leukemia KG1-a cell line. With an IC50 of 25µM, this ciprofloxacin derivative, 7-(4-(2-(benzhydryloxy)-2-oxoethyl) piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4 dihydroquinoline-3- carboxylic acid (4-BHPCP), was an active drug. Through Hoechst 33258 staining and Annexin V/PI double staining experiments, the apoptotic activity of the 4-BHPCP was assessed morphologically. Real-time quantitative PCR was used to assess changes in the expression level of certain apoptosis-related genes, including Bcl-2, Bax, and Survivin (qRT PCR). The results of the qRT PCR analysis demonstrated that 4-BHPCP promotes apoptosis in the KG1-a cell line by down-regulating Survivin and Bcl2, up-regulating Bax, and increasing the Bax/Bcl2 transcripts in a time-dependent manner. These results imply that this novel chemical may be a promising therapy option for acute myeloid leukemia.