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  3. Design, synthesis, biological evaluation and multi spectroscopic studies of novel 2-styrylquinoline-carboxamide derivatives as potential DNA intercalating anticancer agents

Design, synthesis, biological evaluation and multi spectroscopic studies of novel 2-styrylquinoline-carboxamide derivatives as potential DNA intercalating anticancer agents

  • Bioorg Chem. 2025 Jan:154:108098. doi: 10.1016/j.bioorg.2024.108098.
Negar Omidkhah 1,  Amirhosein Gheisari 1,  Sara Rahimzadeh Oskuei 2,  Jamshidkhan Chamani 3,  Farzin Hadizadeh 1,  Amirhosein Atarodi 1,  Razieh Ghodsi 4
Affiliations

Affiliations

  • 1 Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
  • 2 Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
  • 3 Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran.
  • 4 Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: ghodsir@mums.ac.ir.
PMID: 39753040 DOI: 10.1016/j.bioorg.2024.108098
Abstract

In this study, novel 2-styrylquinoline derivatives possessing a planar aromatic system and a flexible side chain with an amino substituent were designed and synthesized as DNA-intercalating antitumor agents. The cytotoxic activity of the synthesized compounds was evaluated against four Cancer cell lines including MCF-7 (breast Cancer cells), A549 (lung epithelial Cancer cells), HCT116 (colon Cancer cells) and normal cell line L929 (mouse fibroblast cell line). The results displayed that the anti-cancer activity of the target quinolines is sensitive to the lipophilic nature of the C-6 and C-7 quinoline substituents. The Anticancer activity of most of the target quinolines against MCF-7 and A549 cells was more than those of HCT116. Compound 3h possessing two methyl groups at the C-6 and C-7 of quinoline ring displayed the most cytotoxicity with IC50 value of 5.7 µM against A549 Cancer cells. Interaction of compound 3h with calf thymus DNA (ctDNA) was investigated by means of UV absorption spectrophotometry, fluorescence spectroscopy, circular dichroism (CD), Resonance light scattering (RLS), viscos metric techniques and also by docking and molecular dynamic studies. RLS intensity, fluorescence quenching of ctDNA and fluorescence quenching EtBr-ctDNA and AO-ctDNA complexes augmented with increasing of compound 3h concentration, significant increasing in viscosity and melting point of ctDNA in the presence of compound 3h, absorbance increasing of ctDNA-compound 3h complex by increasing of NaCl and KI concentrations, higher Ksv value for dsctDNA (3.03 × 104 M-1) compared to ssctDNA (1.31 × 104 M-1), circular dichroism (CD) studies, docking and molecular dynamic studies revealed that compound 3h can interact with ctDNA through intercalation into DNA.

Keywords

2-Styrylquinoline; DNA binding study; DNA intercalating agents; Docking; Molecular dynamics; Quinoline; Spectroscopic studies.

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