Microwave-assisted synthesis and in vitro and in silico studies of pyrano[3,2-c]quinoline-3-carboxylates as dual acting anti-cancer and anti-microbial agents and potential topoisomerase II and DNA-gyrase inhibitors
Abstract
A microwave-assisted method was utilized to synthesize novel pyranoquinolone derivatives as dual acting topoisomerase II/DNA gyrase inhibitors with apoptosis induction ability for halting lung cancer and staphylococcal infection. Herein, the designed rationale was directed toward mimicking the structural features of both topoisomerase II and DNA gyrase inhibitors as well as endowing them with apoptosis induction potential. The absolute configuration of the series was assigned using X-ray diffraction analysis. Cytotoxic activity against NSCLC A549 cells showed that ethyl 2-amino-9-bromo-4-(furan-2-yl)-5-oxo-5,6-dihydro-4H-pyrano[3,2-c]quinoline-3-carboxylate (IC50 ≈ 35 μM) was the most potent derivative in comparison to the positive control Levofloxacin and was selected for further investigation to assess its selectivity (SI = 1.23). Furthermore, in vitro antibacterial screening revealed the potential activity of this bromo derivative against Staphylococcus aureus. Mechanistic studies showed that the aforementioned compound exhibited promising inhibitory activity against topoisomerase II (IC50 = 45.19 μM) and DNA gyrase (IC50 = 40.76 μM) compared to reference standards. In addition, the previous compound induced a A549 cell apoptosis by 38.49-fold and it also increased the total apoptosis by 20.4% compared to a 0.53% increase in the control. Docking simulations postulated its interactions and suggested well fitting into its molecular targets.
Read the paper
Related studies
- Ferulic acid regulates the AKT/GSK-3β/CRMP-2 signaling pathway in a middle cerebral artery occlusion animal model
- Novel Pharmacokinetic/Pharmacodynamic Parameters Quantify the Exposure–Effect Relationship of Levofloxacin against Fluoroquinolone-Resistant Escherichia coli
- Photochemical behavior of levofloxacin
- Correlation Between Dissolution Profiles of Salt-Form Drugs in Biorelevant Bicarbonate Buffer and Oral Drug Absorption: Importance of Dose/ Fluid Volume Ratio
- Evaluation of the synergistic potential and mechanisms of action for de novo designed cationic antimicrobial peptides
- Synthesis of [11C]levofloxacin
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.