Design and synthesis of quinoline-triazole schiff base metal complexes as potential anti-cancer agents

Abstract

The aim of the project was to synthesize quinoline-1,2,3-triazole Schiff base hybrids as promising anti-cancer agents. A laboratory prepared 2-Amino-3,5dibromoactophenone was subjected to Claisen-Schmidt aldol-condensation with benzaldehyde derivatives to form 2-aminochalones. The step was followed by an acid mediated-cyclization reaction to form 2-substituted 2,3-dihydro-quinolin-4(1H)ones, which in turn underwent dehydrogenation and oxidative aromatization to afford 2-substituted quinolin-4(1H)-ones derivatives. The nucleophilic substitution of the latter with sodium azide yielded the 2-substituted 4-azidoquinolines, which underwent Huisgen cycloaddition reaction to form the 4-triazolo-quinoline derivatives in high yields and further confirmed using X-ray diffraction analysis. The 4-triazolo quinoline derivatives formed from propargyl alcohol, served as precursors for oxidation reaction to afford carbaldehyde triazolyl-quinoline derivatives, which in turn were reacted with 2-picolylamine to produce a quinoline-triazolyl Schiff base ligand derivatives in low yields through condensation reaction. The 3-fluoro-phenyl triazole derivatives were subjected to metal coordination with Ruthenium (II) p-cymene bischloride to form ruthenium arene coordinated complexes, showing a CIS in the range of ẟ (-0.003-0.047) ppm for 1H NMR and ẟ (-0.058-0.010 ppm) for 13C NMR. All the synthesised compounds were confirmed using a combination of 1H-NMR, 13C-NMR, FT-IR, and mass spectrometry. The triazolyl quinoline derivative compounds were tested against MDA-MB-231 cell line (breast cancer) here (6,8-dibromo-4-(4-(3fluorophenyl)1H-1,2,3-triazol-1-yl)-2-(4-methoxyphenyl) quinoline 153 h showed a good cytotoxicity effect compared to other compounds with an IC50 of 40.7 µM. The quinoline triazolyl compound molecular docking revealed that(6,8-dibromo-4-(4-(3fluorophenyl)1H-1,2,3-triazol-1-yl)-2-(4-methylphenyl) quinoline 153 g displays good binding energy of -10.9 k calmol and an inhibitory concentration of 0.80 µM against VEGFR-2 tyrosine kinase referenced to Sorafenib (standard).