Investigation of the antiproliferative, cytotoxic and antimicrobial properties of fluorinated salicyladimines

Multidrug resistance to anticancer and antimicrobial drugs has become a global health problem. The antiproliferative, cytotoxic and antimicrobial properties of ten fluorinated Schiff bases were investigated. Doxorubicin (DOX) was used as a positive control in anticancer studies and Gentamicin (GEN) and Ciprofloxacin (CIP) were used positive controls in antimicrobial studies. The cytotoxic effects of compounds on lung adenocarcinoma cell line (A549) and their antimicrobial effects on E. coli, S. aureus, and P. aureginosa were tested b3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Antiproliferative effects were tested by 5(6)-carboxyfluorescein succinimidyl ester (CFSE) staining method. Apoptosis-inducing abilities were tested by Rhodamine 123 (Rod-123)staining and active caspase-3 assay for mitochondrial membrane potential inhibitory effects. Flow cytometric measurements were used in the analysis of CFSE, Rod-123. Flow cytometric measurements and immunofluorescence method were used in the analysis of active-caspase-3 expression. Histopathological changes induced by the compounds in A549 cells were investigated by Hematoxylin & Eosin, Giemsa and Papanicolaou (PAP) protocols. Compound 7 (F2,4,5 SAL: trifluorophenyl) imino) methyl) phenol) exhibited a stronger cytotoxic effect than DOX used as positive control (DOX IC 50: 1.9 µM; Compound 7 IC50: 1.4 µM). The compounds were found to be antiproliferative, inhibit mitochondrial membrane potential and cause the release of active caspase-3. In histopathological examinations, changes such as ghost cells, DNA fragmentation, apoptotic bodies were observed, which supported that apoptosis was effective in cell death. The compounds exhibited lower levels of antimicrobial activity than GEN and CIP and the strongest antimicrobial effect was obtained with Compound 9 (F4 SAL, 2, 3, 5 ve 6tetrafluorophenyl) imino) methyl) phenol MIC50: 18.6 µM) on S. aureus Compound 7, which exhibited a more potent cytotoxic effect than DOX, was found to have the capacity to be an alternative chemotherapeutic agent candidate for in vivo studies