Synthesis, antidiabetic, antioxidant and anti-inflammatory activities of novel hydroxytriazenes based on sulpha drugs

The present study is aimed to investigate the anti-inflammatory, antioxidant and antidiabetic activities of three series of hydroxytriazenes based on sulfa drugs viz; Sulphathiazole (ST), Sulfisoxazole (SF) and Sulphamethoxazole (SM). Antidiabetic activities of the synthesized hydroxytriazenes were investigated by α-glucosidase and α-amylase inhibition method and IC₅₀ values were recorded. The compounds presented significant α-glucosidase and α-amylase inhibition effect with IC₅₀ values ranging from 122 to 341 μg/mL. Anti-inflammatory activity was also investigated by carrageenan-induced paw edema (CPE) method, where % inhibition was up to 89% after 4 h of treatment and antioxidant properties of the similar compounds were assessed by DPPH and ABTS radical scavenging assays. Antioxidant capacity of all the hydroxytriazenes detected by ABTS assay, was significantly higher as compared to DPPH assay. The hydroxytriazenes having highest antioxidant capacity presented IC₅₀ values for compound ST-1 and ST-6 are 488 μg/mL for DPPH, 54.12 μg/mL for ABTS and 858.5 μg/mL for DPPH, 48.0 μg/mL for ABTS, respectively. These results suggested that ABTS assay may be more useful than DPPH assay for synthetic antioxidants. The findings from the molecular docking experiments may also expand the formation of new potent sulpha drugs based hydroxytriazenes targeting towards the subunit of C-terminal of human maltase-glucoamylase for the treatment of diabetes metabolic disorder. Overall, highlight the multifunctional role of hydroxytriazenes as antidiabetic, antioxidant and anti-inflammatory agents.

Keywords: Anti-inflammatory; Antidiabetic activity; Antioxidant; Hydroxytriazenes; Molecular docking; Organic chemistry; Pharmaceutical chemistry; Sulpha drug.