COMPUTATIONAL DESIGN, SYNTHESIS, ANALYSIS AND EVALUATION OF NEW SPIRO [INDOLINE-THIAZOLIDINE] DERIVATIVES FOR ANTI-INFLAMMATORY AND ANTIOXIDANT PROPERTIES

In this study, a series of novel N-(2,4′-dioxospiro[indoline-3,2′-thiazolidin]-3′-yl) isonicotinamide derivatives (VIa-l) were synthesized by cyclizing N1- (2-mercaptoacetyl) isonicotinohydrazide with various 5,6,7-substituted isatins. Structural confirmation of the new compounds was achieved using IR, Mass, H1, and C13 NMR spectroscopy techniques. In-silico molecular docking studies were conducted to identify the binding affinity of the synthesized compounds to the COX-2 enzyme (PDB ID: 3LN1), using PyRx software. The compounds were evaluated for in-vitro and in-vivo anti-inflammatory and antioxidant activities. For the in-vitro anti-inflammatory study, Cayman’s COX (ovine) colorimetric inhibitor screening assay kit was utilized, while for the in-vivo anti-inflammatory activity, the carrageenan-induced rat paw edema method was employed. The in-vitro antioxidant activity of the new derivatives was determined using the DPPH assay method with ascorbic acid as a standard drug. Regarding docking, most compounds exhibited good binding affinity, equal to or greater than that of the standard. All derivatives demonstrated moderate to good anti-inflammatory activity both in-vitro and in-vivo. They showed mild to moderate antioxidant activity compared to ascorbic acid. In conclusion, N-(7 – nitro – 2, 4′- dioxospiro [indoline – 3, 2′-thiazolidin] – 3′-yl) isonicotinamide could be further investigated in search of potent anti-inflammatory agents.