Exploring the therapeutic potential of benzothiazine-pyrazole hybrid molecules against alpha-glucosidase: Pharmacological and molecular modelling based approach

Taj, Saman; Ahmad, Matloob; Alshammari, Abdulrahman; Alghamdi, Abdullah; Ashfaq, Usman Ali

doi:10.1016/j.sjbs.2021.11.033

Cited by 10 publications

(6 citation statements)

References 25 publications

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Section: Pyrazole Derivatives As α‐Glucosidase Inhibitorsmentioning

confidence: 99%

“…Compound 14 with an oxygen atom attached to the benzene ring appeared to have the minimum RMSD (1.222 Å) value and reflected binding interactions with Asp 327 and Arg 526 (Figure 12). [69] A series of newer isatin-pyrazole hybrid derivatives were Arg 171 and Asp 411, respectively. Compound 15a exhibited six hydrogen bonds, while 15b and 15c displayed three and two hydrogen bonds.…”

Section: Pyrazole Derivatives As α-Glucosidase Inhibitorsmentioning

confidence: 99%

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Pyrazole scaffold‐based derivatives: A glimpse of α‐glucosidase inhibitory activity, SAR, and route of synthesis

Firdaus

Siddiqui

Alam

et al. 2023

Archiv der Pharmazie

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The α-glucosidase is a validated target to develop drugs for treating type 2 diabetes mellitus. The existing α-glucosidase inhibitors have certain shortcomings related to side effects and route of synthesis. Accordingly, it is inevitable to develop new chemical templates as α-glucosidase inhibitors. Pyrazole derivatives have a special place in medicinal chemistry because of various biological activities. Recently, pyrazole-based heterocyclic compounds have emerged as a promising scaffold to develop α-glucosidase inhibitors. This study focuses on the recently reported pyrazole-based α-glucosidase inhibitors, including their biological activity (in vivo, in vitro, and in silico), structure-activity relationship, and ways of synthesis. The literature revealed the development of several promising pyrazole-based α-glucosidase inhibitors and new synthetic routes for their preparation. The encouraging α-glucosidase inhibitory results of the pyrazole-based heterocyclic compounds make them an attractive target for further research. The authors also foresee the arrival of the pyrazole-based α-glucosidase inhibitors in clinical practice.

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Section: Pyrazole Derivatives As α‐Glucosidase Inhibitorsmentioning

confidence: 99%

Section: Pyrazole Derivatives As α-Glucosidase Inhibitorsmentioning

confidence: 99%

Pyrazole scaffold‐based derivatives: A glimpse of α‐glucosidase inhibitory activity, SAR, and route of synthesis

Firdaus

Siddiqui

Alam

et al. 2023

Archiv der Pharmazie

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“…highlighted the ability of hybrid compounds made of benzothiazine and pyrazole to prevent α‐glucosidase inhibition. Compound 130 (Figure 22) revealed more active against α‐glucosidase inhibition with IC 50 : 5.8 μM as compared to standard acarbose with IC 50 : 58.8 μM and demonstrated superior efficacy in reducing blood glucose levels in comparison to acarbose and H‐bond interactions included Arg526, Asp 327 [135] . Fatima rashid et al.…”

Section: Discussionmentioning

confidence: 99%

“…Compound 130 (Figure 22) revealed more active against α-glucosidase inhibition with IC 50 : 5.8 μM as compared to standard acarbose with IC 50 : 58.8 μM and demonstrated superior efficacy in reducing blood glucose levels in comparison to acarbose and H-bond interactions included Arg526, Asp 327. [135] Fatima rashid et al reported synthesis and pharmacological evaluation of substituted acetamide derivatives as antidiabetic agents against α-glucosidase and α-amylase inhibition. Compound 131 exhibited potent activity with α-glucosidase and α-amylase inhibition with IC 50 : 5.17 � 0.28 μM and IC 50 : 18.82 � 0.89 μM as compared to standard acarbose with IC 50 : 10.12 � 0.42 μM and IC 50 : 58.8 � 2.69 μM.…”

Section: Synthetic Routes For Benzothiazine Derivativesmentioning

confidence: 99%

Recent Studies of Nitrogen and Sulfur Containing Heterocyclic Analogues as Novel Antidiabetic Agents: A Review

Gharge,

Alegaon

2024

Chemistry & Biodiversity

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The prevalence of diabetes mellitus is on the rise, which demands for the identification of novel antidiabetic drugs. There is a need for safer and more effective alternatives because the therapy methods now available to manage diabetes have limits. Due to their diverse pharmacological characteristics, heterocyclic molecules with nitrogen and Sulfur atoms have become intriguing candidates in medicinal chemistry. These substances have a wide variety of structures that can be customized to target different pathways associated with diabetes and can affect important biological targets involved in glucose homeostasis. This review provides a thorough summary of the most recent studies on heterocyclic analogues of nitrogen and Sulfur as prospective antidiabetic agents. This review examines the variety of their structural forms, their methods of action, and assesses the results of preclinical and clinical investigations on their effectiveness and safety. Additionally, further optimization and development of innovative antidiabetic medications are highlighted, as well as the difficulties and prospects for the future in utilizing the therapeutic potential of these analogues. This study seeks to stimulate additional investigation and cooperation between researchers and medicinal chemists, promoting improvements in the creation of efficient and secure antidiabetic medicines to fulfil the needs in the management of diabetes.

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“…Physicochemical parameters such as molecular mass, log P water (miLogP), the number of OH − , and H + were analyzed via swissADME software ( http://www.swissadme.ch/ ) to evaluate the remedy ability of the best-docked ligand models. 31 , 32 The pharmaceutical drug properties of the synthetic compound FA2 were evaluated according to the Lipinski’s rule of five (RO5). 33 …”

Section: Methodsmentioning

confidence: 99%

Design, Synthesis and Pharmacological Evaluation of 2-(3-BenzoyI-4-Hydroxy-1,1-Dioxido-2H-Benzo[e][1,2]thiazin-2-yI)-N-(2-Bromophenyl) Acetamide as Antidiabetic Agent

Rashid¹,

Ahmad²,

Ashfaq³

et al. 2022

DDDT

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Purpose The present study is based on screening new and potent synthetic heterocyclic compounds as anti-diabetic drugs using various computational tools, lab experiments, and animal models. Methods A potent synthetic compound 2-(3-benzoyl-4-hydroxy-1,1-dioxido-2 H -benzo[ e ][1,2]thiazin-2-yl)-1-(2-bromophenyl) acetamide (FA2) was checked against diabetes and screened via enzyme inhibition assays, enzyme kinetics against alpha-glucosidase and alpha-amylase. Protein–ligand interaction was analyzed via molecular docking and toxicological analysis via ADMET. Experimental animals were used to examine the compound FA2 safety, delivery, and check various biochemical tests related to diabetes like fasting glucose sugar, cholesterol, triglyceride, HbAc1, creatinine, and insulin level. Histography of liver, kidney, and pancreas was also performed. Results Results showed that FA2 had binding energy of ‐7.02 Kcal/mol and ‐6.6 kcal/mol against α‐glucosidase (PDB ID: 2ZE0) and α‐amylase (PDB ID: 1B2Y), respectively. Moreover, in vitro enzyme inhibition assays and enzyme kinetics against α‐glucosidase and α‐amylase were performed, and FA2 showed IC50 at 5.17 ± 0.28 µM and 18.82 ± 0.89 µM concentrations against α‐glucosidase and α‐amylase, respectively. Kinetics studies showed that the FA2 compound impeded α‐glucosidase and α-amylase as a non-competitive mode of inhibition with Ki’ values −0.320 ± 0.001 and 0.141 ± 0.01, respectively. FA2 was further analyzed on alloxan-induced mice for 21 days. Biochemical tests (fasting glucose sugar, cholesterol, triglyceride, HbAc1, creatinine, and insulin levels) and histological examination of liver and kidney showed that the FA2 compound showed better results than acarbose. Histology of pancreas found to show the maintenance of normal pancreatic acini and Langerhans islets in FA2 treated mice compared to acarbose and nontreated diabetic controls. Conclusion Investigating anti-diabetic potential of FA2 compound showed that the selected benzothiazine derivative has tremendous importance in reducing dose concentration and side effects.

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Exploring the therapeutic potential of benzothiazine-pyrazole hybrid molecules against alpha-glucosidase: Pharmacological and molecular modelling based approach

Cited by 10 publications

References 25 publications

Pyrazole scaffold‐based derivatives: A glimpse of α‐glucosidase inhibitory activity, SAR, and route of synthesis

Pyrazole scaffold‐based derivatives: A glimpse of α‐glucosidase inhibitory activity, SAR, and route of synthesis

Recent Studies of Nitrogen and Sulfur Containing Heterocyclic Analogues as Novel Antidiabetic Agents: A Review

Design, Synthesis and Pharmacological Evaluation of 2-(3-BenzoyI-4-Hydroxy-1,1-Dioxido-2H-Benzo[e][1,2]thiazin-2-yI)-N-(2-Bromophenyl) Acetamide as Antidiabetic Agent

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