Antibacterial, cytotoxic and genotoxic activity of nitrogenated and haloid derivatives of C50-C60 and C70-C120 polyprenol homologs.

BACKGROUND: Polyprenol is an important lipid with many bioactive effects. The study on differences in bioactive effects of polyprenol derivatives having different isoprene units are seldom reported and it is helpful to find out which type of polyprenol derivatives are effective for treating A549/HepG2 cells and E. coli /S. aureus. METHODS: All tested polyprenol derivatives were measured with inhibition halos by Oxford cup assays. MIC values were assessed by the broth dilution method. Time-killing curve studies were conducted in duplicate on separate days. Cytotoxicity study was measured by the MTT assay and genotoxic study was evaluated by comet assay. RESULTS: With regard to antibacterial activity, the sensitivities to the quaternary polyprenyl ammonium salt derivatives GAS and MAS were 31.3 µg/mL and 15.6-31.3 µg/mL, respectively. GAS and MAS exhibited cytotoxic activity toward HepG2 cells (IC50 of 10.1-11.6 µg/mL), which was stronger than that exhibited toward A549 cells (IC50 of 13.8-13.9 µg/mL). The bactericidal activity of MAS was stronger than that of GAS at the same concentration at least 48 h. The DNA damage in A549 and HepG2 cells exposed to all 10, 20 and 40 µg/mL MAS was statistically significant in comparison to the control. Our results indicate a dose-dependent increment in DNA damage in A549 and HepG2 cells exposed to 10, 20 and 40 µg/mL MAS for both the percentage of DNA in the tail and tail moment. CONCLUSION: The quaternary ammonium salt derivatives GAS and MAS exhibited higher antibacterial (E. coli and S. aureus) and cytotoxic activity (A549 and HepG2 cells) than the other derivatives evaluated in this study. The DNA damage in HepG2 cells suggests that MAS induced A549 and HepG2 cells death via apoptotic pathway. Our results provide new evidence supporting the medical use of polyprenol derivatives against bacterial and tumor diseases.