New Biologically Hybrid Pharmacophore Thiazolidinone-Based Indole Derivatives: Synthesis, In Vitro Αlpha-Amylase and Αlpha-Glucosidase Along with Molecular Docking Investigations

Abstract

Amylase and glucosidase enzymes are the primary harmful source in the development of the chronic condition known as diabetes mellitus. The main function of these enzymes is to break the macromolecules into simple sugar units which are directly involved in the solubility of blood, hence increasing blood glucose levels. To overcome this effect, there is a need for a potent and effective inhibitor that inhibits the conversion of macromolecules of sugar into its smaller units. In this regard, we synthesized thiazolidinone-based indole derivatives (1–20). The synthesized derivatives were evaluated for α-amylase and α-glucosidase inhibitory activity. Different substituted derivatives were found with moderate to good potentials having IC50 values ranging, for α-amylase, from 1.50 ± 0.05 to 29.60 ± 0.40 μM and, for α-glucosidase, from IC50 = 2.40 ± 0.10 to 31.50 ± 0.50 μM. Among the varied substituted compounds, the most active analogs four (1.80 ± 0.70 and 2.70 ± 0.70), five (1.50 ± 0.05 and 2.40 ± 0.10, respectively) of the series showed few folds better inhibitory activity than standard drug acarbose (IC50 = 10.20 ± 0.10 and 11.70 ± 0.10 μM, respectively). Moreover, structure–activity relationship (SAR) was established and binding interactions were analyzed for ligands and proteins (α-amylase and α-glucosidase) through a molecular docking study.

Blood indices of omega-3 and omega-6 polyunsaturated fatty acids are altered in hyperglycemia

“…Burgeoning evidence thus necessitates the integration of microbiome studies with the risk of DM and related complications, most notably dyslipidemia and anemia ( Alfhili et al, 2022c ). Further characterization of novel compounds with anti-α-glucosidase activity is equally important ( Hussain et al, 2022 , Khan et al, 2022 , Mumtaz et al, 2022 ).…”

α‐Amylase Inhibitors Based on Thiazolidinone Skeleton: A Promising Approach in Diabetes Management

“…Indole-linked derivatives of thiazolidinone 31 a-t were synthesized and tested for their in vitro α-amylase and αglucosidase inhibitory potential by Khan and coauthors. [88] Tested analogs exhibited good to moderate potential, while compounds In another work, Khan and coauthors [89] synthesized benzothiazole clubbed thiazolidinone derivatives 32 a-o and evaluated them for antidiabetic potential using α-amylase and glucosidase enzymes. Compounds were found to show notice-able potency, while compounds 32 d (IC 50 = 2.40 and 3.50 μM), 32 e (IC 50 = 2.30 and 4.80 μM), and 32 f (IC 50 = 2.10 and 3.20 μM) were found more effective than reference, Acarbose (IC 50 = 9.10 and 10.70 μM).…”

“…Indole‐linked derivatives of thiazolidinone 31 a – t were synthesized and tested for their in vitro α‐amylase and α‐glucosidase inhibitory potential by Khan and coauthors [88] . Tested analogs exhibited good to moderate potential, while compounds 31 d (IC 50 =1.80 and 2.70 μM) and 31 e (IC 50 =1.50 and 2.40 μM) showed more potent inhibition than standard, Acarbose (IC 50 =10.20 and 11.70 μM).…”

Design, Synthesis, and Molecular Docking Studies of Integrated Benzylidenethiazolidine‐2,4‐Dione and Thieno[2,3‐d]pyrimidine‐6‐Carboxylate Derivatives as Potent Antidiabetic agents

“…[3] Over the past two decades, various thiophene-fused pyrimidine scaffolds have been developed and synthesized as drug-like candidates for a variety of pharmacological applications, particularly as adenosine receptor ligands. [4,5] Further, since purine and pyrimidine bases are structural elements of double-stranded nucleic acids, many fused pyrimidines and purines have been considered for integration through medicinal chemistry approaches to design effective therapeutic agents. As well, pyridines, purines and pyrimidines are other examples of biologically active cyclic nitrogen heterocycles.…”

“…For example, thienopyrimidine and thiazolidinediones are the important nitrogen‐ and sulfur‐containing heterocyclic derivatives known as potential candidates for anti‐diabetic and anticancer activities [3] . Over the past two decades, various thiophene‐fused pyrimidine scaffolds have been developed and synthesized as drug‐like candidates for a variety of pharmacological applications, particularly as adenosine receptor ligands [4,5] . Further, since purine and pyrimidine bases are structural elements of double‐stranded nucleic acids, many fused pyrimidines and purines have been considered for integration through medicinal chemistry approaches to design effective therapeutic agents.…”