Ag NPs on chitosan-alginate coated magnetite for synthesis of indazolo[2,1-b]phthalazines and human lung protective effects against α-Guttiferin

Abstract

Biocomposite nanomaterials have been evolved as the new generation catalysts and therapeutic supplement in these days. Magnetically isolation has added new features to this category. This has encouraged us to synthesize a novel Ag NP adorned chitosan-alginate dual bio-polysaccharide (two of the more versatile polysaccharides) modified core-shell magnetic nanocomposite (Fe3O4/CS-Alg/Ag NPs). The material was meticulously characterized following different physicochemical techniques, such as, FT-IR, ICP-OES, FESEM, EDX, atomic mapping, TEM, VSM, XRD and XPS studies. The as synthesized material was catalytically explored in the one-pot multicomponent synthesis of biologically potent 2H-indazolo[2,1-b]phthalazine-trione derivatives involving a wide range of substrates. The reactions were ended up with excellent yields under solvent-free heating conditions. The catalyst recyclability, heterogeneity and leaching tests were performed to ensure its high stability and robustness. It could be reused as much as 10 times in succession with almost unchanged catalytic performances. In the lung protective part of the present research, the human lung toxicity was induced by α-Guttiferin. The cell viability of lung MRC-5, CCD19Lu, WI-38, and BEAS-2B cell lines was measured by trypan blue assay. Caspase-3 activity was assessed by the caspase activity colorimetric assay kit and mitochondrial membrane potential of lung cells was studied by Rhodamine123 fluorescence dye. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) test was used to show DNA fragmentation and apoptosis of lung cells. Also, the Rat inflammatory cytokine assay kit was used to measure the concentrations of inflammatory cytokines. The catalyst-treated cell cutlers significantly (p ≤ 0.01) reduced the DNA fragmentation, caspase-3 activity, and inflammatory cytokines concentrations, and raised the mitochondrial membrane potential and cell viability in the high concentration of α-Guttiferin-treated lung MRC-5, CCD19Lu, WI-38, and BEAS-2B cells. The best result of lung protective properties of catalyst against α-Guttiferin was seen in the high dose of catalyst i.e., 4 μg. DPPH test revealed similar antioxidant potentials for catalyst and butylated hydroxytoluene. The catalyst inhibited half of the DPPH molecules in the concentration of 171 μg/mL. According to the above results, catalyst can be administrated as a lung protective drug for the treatment of lung diseases after approving in the clinical trial studies in humans.