Journal Article Epublish
PubMed: 39839233 DOI: 10.1039/d4ra06201a
Microwave-assisted synthesis and and studies of pyrano[3,2-]quinoline-3-carboxylates as dual acting anti-cancer and anti-microbial agents and potential topoisomerase II and DNA-gyrase inhibitors.
RSC Adv 15(3):1941-1956
Authors: Ashraf A Aly, Hisham A Abd El-Naby, Essam Kh Ahmed, Sageda A Gedamy, Kari Rissanen, Martin Nieger, Alan B Brown, Michael G Shehat, Marwa M Shaaban, Amal Atta
Affiliations
- Chemistry Department, Faculty of Science, Minia University 61519 El-Minia Egypt.
- Department of Chemistry, University of Jyväskylä P. O. Box 35 FIN-40014 Jyväskylä Finland.
- Department of Chemistry, University of Helsinki P. O. Box 55, A. I. Virtasen aukio I 00014 Helsinki Finland.
- Department of Chemistry and Chemical Engineering, Florida Institute of Technology Melbourne FL 32901 USA.
- Department of Microbiology, Faculty of Pharmacy, Alexandria University Alexandria 21521 Egypt.
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University Alexandria 21521 Egypt.
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-4-pyrano[3,2-]quinoline-3-carboxylate (IC ≈ 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, antibacterial screening revealed the potential activity of this bromo derivative against . Mechanistic studies showed that the aforementioned compound exhibited promising inhibitory activity against topoisomerase II (IC = 45.19 μM) and DNA gyrase (IC = 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.
MeSH
Cells, A549 Cells, Neoplasms, Dna Gyrase, Apoptosis, Dna Topoisomerases, Type Ii, Dna