Synthesis, anticancer evaluation, and molecular docking study of novel 4‐hydroxybenzo[h][1,6]naphthyridine‐2,5‐dione derivatives

Abstract

An operationally efficient and affordable lactone-to-lactam transformation was designed from pyrano [3,2-c]quinolinone 1 to obtain 4-hydroxybenzo [h][1,6] naphthyridine-2,5-dione 2 utilizing ammonium acetate. The newly synthesized compound 2 was subjected to different electrophilic substitution reactions such as nitration, chlorination, bromination, and N-acylation to obtain novel benzo [h][1,6]naphthyridine derivatives with different substituents at C-3, C-4, and NH. Structures of novel products were achieved by elemental analyses and spectroscopic techniques. The benzonapthyridine derivatives were screened for their antitumor activities against some cancer cell lines including HepG-2, HCT-116, and MCF-7. All the examined compounds revealed strong, good, moderate to weak anticancer activity compared with 5-fluorouracil as a reference standard. Compound (3, -3NO 2 ) was the most cytotoxic one and exhibited a higher inhibitory activity than the standard drug against HCT-116 and MCF-7 with IC 50 values of 20.7 ± 1.9 and 22.5 ± 2.1 μg/ml, respectively, and strong activity against HepG-2 with IC 50 = 15.3 ± 0.7 μg/ml. Moreover, a molecular docking study was carried out for the tested compounds against the crystallographic structure of the Topo II enzyme as a potential target to investigate their binding modes. Docking results showed that compound 6b fitted well into the active site of topoisomerase II (PDB ID: 1ZXM) with hydrogen bond interactions.

Structure, properties, and thermal behavior of chemically synthesized 3-((2,5 Difluorophenyl)diazenyl)-6-ethyl-4-hydrox-2H-pyrano[3,2-c]quinoline-2,5(6H)-dione as new brand organic materials: Antimicrobial activity

“…Some recent studies depicted that compounds containing fluorine atoms (an electron-withdrawing group) strengthen the inhibitory activity of cancer cells [40,71,72]. This may be due to the high electronegativity of fluorine atoms (4.0 on Pauling's electronegativity scale) which causes increasing the lipophilicity of the molecule that enhances the absorption rate, and helps easy penetration of the compound through the lipid membranes and therefore boosts the intercellular drug delivery [40,73,74]. In conclusion, DFPDAEHPQD was successfully synthesized and characterized by various elemental analyses, FTIR, TGA, and XRD techniques.…”