Antiproliferative Activity of Antibiotics through DNA Binding Mechanism: Evaluation and Molecular Docking Studies.
Alexandros-Dimitrios C MagklarasChristina N BantiSotiris K HadjikakouPublished in: International journal of molecular sciences (2023)
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 ( CIP·HCl ), penicillin G sodium salt ( PEN·Na ), and tetracycline hydrochloride ( TC·HCl ) was determined by UV-Vis spectra and viscosity measurements. Furthermore, their binding constants ( K b ) toward CT-DNA were calculated ( K b = (2.8 ± 0.6) × 10 4 ( CIP·HCl ), (0.4 ± 0.1) × 10 4 ( PEN·Na ) and (6.9 ± 0.3) × 10 4 ( TC·HCl ) Μ -1 ). 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 50 values: 417.4 ± 28.2 ( CIP·HCl ), >2000 ( PEN·Na ) and 443.1 ± 17.2 ( TC·HCl ) 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 ( DOX ). Despite their low binding affinity to DNA ( K b ) or their different mode of interaction, TC·HCl (anthracycline) or CIP·HCl (quinolones), exhibit notable antiproliferative activity and low toxicity.
Keyphrases
- cell cycle arrest
- cell death
- circulating tumor
- dna binding
- molecular docking
- induced apoptosis
- cell free
- pi k akt
- single molecule
- endothelial cells
- squamous cell carcinoma
- molecular dynamics simulations
- oxidative stress
- transcription factor
- nucleic acid
- case control
- endoplasmic reticulum stress
- magnetic resonance imaging
- pseudomonas aeruginosa
- molecular dynamics
- induced pluripotent stem cells
- drug delivery
- cystic fibrosis
- image quality
- small molecule
- positron emission tomography
- mass spectrometry
- protein protein
- oxide nanoparticles