Synthesis, Antioxidant and Anti-proliferative Activity of Novel Pyridonaphthyridines: Multicomponent Reactions of Electron Deficient Acetylenic Compounds

Abstract In this investigation, we successfully synthesized fused pyridonaphthyridines, a newly identified class of fused heterocyclic compounds, through an efficient multicomponent reaction. The methodology involved utilizing 3-(2-hydroxyphenyl)-3-iminopropanamide, 2-(1,3-diimino-1,3-dihydro-2H-inden-2-ylidene) malononitrile, alkyl bromides, and activated acetylenic derivatives within an aqueous medium at ambient temperature. Notably, the process was facilitated by a reusable catalyst composed of Ag/Fe3O4@GO. The newly synthesized compounds were subsequently evaluated for their antiproliferative potential against MCF-7 breast cancer and HCT-15 colon cancer cell lines using the Sulfo-rhodamine B (SRB) assay, along with their antioxidant capabilities. Among the compounds tested, derivatives 5c and 5 g demonstrated notably superior antiproliferative activity relative to their counterparts. To further explore their interaction with biological macromolecules, these two compounds underwent UV-Vis spectral analysis to determine their binding affinities to DNA and bovine serum albumin (BSA). The results revealed affinity constants of K5c-DNA = 7.32 × 10³ M−1, K5g-DNA = 2.09 × 104 M−1, K5c-BSA = 5.32 × 104 M−1, and K5g-BSA = 8.24 × 104 M−1, respectively. The outcomes of this study could provide novel insights into the relationship between the chemical structure of these pyridonaphthyridine analogs and their capacity to inhibit cancer cell proliferation. Graphical Abstract