Laboratory of Biological Inorganic Chemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece.
Int J Mol Sci. 2023 Jan 29;24(3):2563. doi: 10.3390/ijms24032563.
The antiproliferative activity of three antibiotics clinically use, was studied through DNA inhibition mechanisms, ex vivo, in silico and in vitro. The ex vivo interaction of DNA with ciprofloxacin hydrochloride (), penicillin G sodium salt (), and tetracycline hydrochloride () was determined by UV-Vis spectra and viscosity measurements. Furthermore, their binding constants () toward CT-DNA were calculated ( (2.8 ± 0.6) × 10 (), (0.4 ± 0.1) × 10 () and (6.9 ± 0.3) × 10 () Μ). Docking studies on the binding interactions of antibiotics with DNA were performed to rationalize the ex vivo results. The in vitro antiproliferative activity of the antibiotics was evaluated against human breast adenocarcinoma (MCF-7) cells (IC values: 417.4 ± 28.2 (), >2000 () and 443.1 ± 17.2 () μΜ). Cell cycle arrest studies confirmed the apoptotic type of MCF-7 cells. The toxicity of the studied agents was in vitro tested against human fetal lung fibroblast cells (MRC-5). The results are compared with the corresponding one for doxorubicin (). Despite their low binding affinity to DNA () or their different mode of interaction, (anthracycline) or (quinolones), exhibit notable antiproliferative activity and low toxicity.
三种临床上常用抗生素的抗增殖活性通过 DNA 抑制机制，在离体、在体和体外进行了研究。通过紫外-可见光谱和粘度测量，确定了盐酸环丙沙星（）、青霉素 G 钠盐（）和盐酸四环素（）与 DNA 的离体相互作用。此外，还计算了它们与 CT-DNA 的结合常数（（2.8 ± 0.6) × 10（）、（0.4 ± 0.1) × 10 () 和 (6.9 ± 0.3) × 10 () Μ)。进行了抗生素与 DNA 结合相互作用的对接研究，以合理化离体结果。抗生素对人乳腺癌腺癌细胞（MCF-7）的体外抗增殖活性进行了评估（IC 值：417.4 ± 28.2 (), >2000 () 和 443.1 ± 17.2 () μΜ)。细胞周期阻滞研究证实了 MCF-7 细胞的凋亡类型。研究药物的体外毒性针对人胎儿肺成纤维细胞（MRC-5）进行了测试。结果与多柔比星（）的相应结果进行了比较。尽管它们与 DNA 的结合亲和力低（）或相互作用方式不同，但 （蒽环类药物）或 （喹诺酮类）表现出显著的抗增殖活性和低毒性。
