Synergistic Effects of IMP-1700, Ciprofloxacin, and X-Ray Radiation in Bacteria and Mammalian Cell Lines: Implications for Use in Antimicrobial-Resistant Bacteria.

IMP-1700 was developed as a compound designed to target bacterial DNA repair-associated pathways, including homologous recombination mediated by the AddAB/RecBCD system. While its antibacterial properties are well established, the potential effects on mammalian noncancerous and tumor cells under genotoxic stress remain to be elucidated. This study investigates the impact of IMP-1700 and its synergistic effect in combination with ciprofloxacin (CPX) and X-ray radiation in bacterial cultures and mammalian cell lines. In Staphylococcus aureus (S. aureus), neither IMP-1700 (5 µM) nor CPX (15 µM) as monotherapy significantly reduced bacterial growth; their combination produced a substantial reduction in bacterial counts, and IMP-1700 further enhanced killing when combined with 10 Gy X-ray irradiation, resulting in a 77% decrease, demonstrating synergistic antibacterial activity. In mammalian cells, X-ray cytotoxicity was cell-type dependent: noncancerous NIH-3T3 fibroblasts showed no significant effect, while B16.F10 melanoma cells displayed delayed sensitivity, MDA-MB-231 breast cancer cells an intermediate response, and HepG2 hepatocellular carcinoma cells marked radioresistance. IMP-1700 enhanced radiation-induced cytotoxicity across all cell lines, particularly at 72 h post-irradiation. These findings suggest that although IMP-1700 was designed to target bacterial DNA repair pathways, it can enhance sensitivity to genotoxic stress in both bacterial and mammalian systems. Further mechanistic investigation and safety evaluation are required before potential therapeutic application.