Hydroxytriazenes incorporating sulphonamide derivatives: evaluation of antidiabetic, antioxidant, anti-inflammatory activities, and computational study.

The existent investigation deals with synthesis, characterization, computational analysis, and biological activities of some hydroxytriazene derivatives containing sulphonamide moiety. The compounds were screened for antidiabetic, antioxidant, and anti-inflammatory activities. The antidiabetic activity was assessed using α-glucosidase and α-amylase inhibition assays with IC50 values ranging from 32.0 to 759.13 µg/mL and 157.77 to 340.47 µg/mL while standard drug acarbose showed IC50 values 12.21 and 69.74 µg/mL, respectively. The antioxidant activity was evaluated using DPPH and ABTS radical scavenging assays with IC50 value ranging from 54.01 to 912.66 µg/mL and 33.22 to 128.11 µg/mL, and standard drug ascorbic acid showed IC50 values 29.12 µg/mL and 69.13 µg/mL, respectively. Anti-inflammatory activity was investigated using the carrageenan-induced paw edema method, where percentage inhibition was up to 93.0 and 98.57 for 2 h and 4 h, respectively, and all the compounds were found to exhibit excellent anti-inflammatory activity. Moreover, prediction of activity spectra for substance and molecular docking were also performed. The PASS prediction hypothesized the potential of the compounds for anti-inflammatory activity, and docking results suggested the best binding pose for compounds 1b and 2b with the least energy value from which compounds can be considered as potent COX-2 inhibitors. Furthermore, possible interactions between hydroxytriazene analogues and the targets of antioxidant NADPH oxidase and antidiabetic human maltase-glucoamylase enzyme have been identified. The HOMO and LUMO analysis revealed charge transfer within the compounds. These findings suggested that the synthesized compounds can be potential agents for the treatment of diabetes and inflammation.

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.

Synthesis of Some New Hydroxytriazenes and their Antimicrobial and Anti-inflammatory Activities.

BACKGROUND: Hydroxytriazenes and their derivatives have been studied for the biological and pharmacological applications in the past few years. These compounds possess antibacterial, antifungal, anti-inflammatory, analgesic and wound healing activities. In this study, we report the synthesis of ten hydroxytriazenes in two series derived from disubstituted aniline and studied for antimicrobial and anti-inflammatory activities. METHODS: For this purpose, 2-methyl-5-chloroaniline and 2-trifluoromethyl-5-chloroaniline were used to synthesize compounds A1-5 and B1-5 series, respectively. All compounds were synthesized by the reported method which involves three steps of the method (i) Reduction, (ii) Diazotization, (iii) Coupling. All synthesized compounds were characterized by various techniques CHN elemental analysis, FTIR, 1H NMR, and MASS spectral analysis. The antibacterial activities of the compounds were screened against S. aureus, S. pyogenes, E. coli, P. aeruginosa, and antifungal activities were against C. albicans, A. clavatus by the zone of inhibition method. In addition, anti-inflammatory activity was also evaluated by carrageenan-induced paw edema method and results were reported as % inhibition. RESULTS: All the synthesized compounds were obtained in pure form and their spectral data are in good agreement with their structure. The synthesized compounds have shown good antimicrobial activity and zone of inhibition was ranging 21 to 24 mm. Further antiinflammatory effect of the compounds was 96.58 to 98.71 % inhibition. CONCLUSION: The results of the present study indicate that chloro and trifluoromethyl substitution at hydroxytriazenes skeleton could improve anti-inflammatory and antimicrobial activities.