A series of pyrazole-Schiff base derivatives, 3a-i, were synthesized by reacting arylamines 2a-i with pyrazole aldehyde 1, utilizing two catalysts: ammonium chloride (catalystA) or acetic acid (catalystB). The compounds were analyzed using spectroscopic methods, including 1H and 13C NMR, along with high-resolution mass spectrometry. Their antidiabetic and antioxidant activities were assessed through various in vitro assays, encompassing evaluation of inhibitory effects on α-glucosidase, α-amylase enzymes and determination of reducing power, free radical scavenging activity. The most promising in vitro antidiabetic results were also observed with analogs 3c (α-amylase IC50 = 19.57 ± 0.07 µM, α-glucosidase IC50 = 17.13 ± 0.28 µM) and 3h (α-amylase IC50 = 22.50 ± 0.06 µM, α-glucosidase IC50 = 20.75 ± 0.17 µM). Both products 3c and 3h revealed activity near to the standard acarbose (IC50 (α-amylase) =16.28 ± 0.24 µM, IC50 (α-glucosidase) =13.19 ± 0.26 µM). Among all compounds, 3c and 3h exhibited the highest transition metal reducing activity at levels of 75.27 ± 1.99 and 78.42 ± 0.58 µM Trolox equivalents (TE), respectively, along with the most significant free radical scavenging effects at levels of 73.79 ± 0.11 and 72.98 ± 0.33 µM TE, respectively. The antioxidant results of the current set of pyrazole-Schiff base derivatives 3a–i indicated their potential benefits as free radical scavenging and metal-reducing agents, thus proving their antioxidant capability. Their higher antidiabetic and antioxidant activities compared to other compounds might be explained by the presence of a free phenolic hydroxy group in 3c and a benzothiazole motif in 3h. These findings also lend support to the multifaceted biological functions associated with their antidiabetic activity, including their antioxidant activity. In silico molecular docking studies confirm the antihyperglycemic impact, elucidating the nature of interactions between 3c and 3h and HPA/HLAG catalytic sites.
Read full abstract