Schiff Bases of Pioglitazone Provide Better Antidiabetic and Potent Antioxidant Effect in a Streptozotocin–Nicotinamide-Induced Diabetic Rodent Model

Abstract

Pioglitazone is a Food and Drug Administration-approved thiazolidinedione (TZD) derivative and peroxisome proliferator-activated receptor gamma (PPARγ) agonist and used for the treatment of diabetes mellitus (DM). However, this drug is still associated with many adverse effects. In the present study, four new Schiff bases of pioglitazone (P1–P4) were synthesized and characterized using FTIR, 1 HNMR, 13 CNMR, mass spectrometry, and elemental analysis. For preliminary screening, the in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and in vitro alpha-amylase antidiabetic inhibitory assay were performed. Further, P3 was used to investigate in vivo antioxidant and in vivo antidiabetic effects in a streptozotocin–nicotinamide-induced diabetic rat model. Diabetic rats were administered with an i.p dose of pioglitazone 10 mg/kg body weight for 21 days. Moreover, biochemical parameters and antioxidants were quantified from liver and kidney tissues of rodents. In the DPPH assay, compound P3 showed superior antioxidant effects. Using the in vitro α-amylase inhibitory assay, P3 exhibited potent effects as compared to other groups, that is, 93% inhibition, while pioglitazone showed 81% inhibition. Enzymatic and nonenzymatic antioxidants showed significant changes in P3 (10 mg/kg)-treated groups ( p < 0.001). Similarly, compound P3 produced significant and better results in comparison to pioglitazone in the rodent model. This study confirmed potent antidiabetic and superior antioxidant potential of the newly synthesized Schiff base (P3), which could ultimately account for insulin sensitization and for cellular protection and hence provide a potential clue for dual therapeutics.

Step‐Economical Mechanosynthesis of Hybrid Azoles: Deciphering Their π‐Orbital and Pharmacological Characteristics

“…[58,59] Similarly, different thiazolidinone-based pharmacophores were documented to exhibit antihyperglycemic activity. [60,61] For instance, a series of triazole tethered amino acid derivatives were found to exhibit hyperglycemia inhibition at a dose level of 40 mg/kg body weight. [60] Similarly, α-amylase inhibitory effect of thiazolidinedione-Schiff base conjugates with IC 50 values ranging from 14.7 to 47.44 μM were also reported.…”

Metal Complexes with Schiff Bases: Data Collection and Recent Studies on Biological Activities

“…In addition to their usefulness in catalysis [ 1 ], they showed diverse biological activities [ 2 , 3 ] including antimicrobial [ 4 ], antiproliferative [ 5 ], antimalarial [ 6 , 7 ], analgesic, anxiolytic [ 8 ], antidepressant [ 9 ], anti-inflammatory [ 10 , 11 ], antiviral [ 12 ], antipyretic, antibacterial [ 13 ] and antifungal [ 14 ]. Moreover, several studies on SBs-metal complexes showed their use as anti-Alzheimer agents [ 15 , 16 , 17 ], and their potential in the management of diabetes mellitus [ 18 ]. Some SBs derivatives have demonstrated α-glucosidase inhibition and antiglycation activity [ 19 , 20 ], whereas other derivatives were synthesized and used as fluorescent sensors for the diabetic biomarker beta-hydroxybutyrate (β-HB) [ 21 ].…”

Synthesis, crystal structure, and antidiabetic property of hydrazine functionalized Schiff base: 1,2-Di(benzylidene)hydrazine

“…Diabetes mellitus, one of the global health issues, is due to irregular insulin production that can lead to a series of other diseases. Recently, functionalized Schiff bases are found to be a promising candidate in this field [31]. In various studies conducted to investigate insulin-mimetic properties, hydrazine derivatives of Schiff base have some interesting results, for example, Szklarzewick's group showed the antidiabetic potentiality of a Schiff base [32].…”