2‐Chloroquinolinyl‐thiazolidine‐2,4‐dione Hybrids as Potential α‐Amylase Inhibitors: Synthesis, Biological Evaluations, and In Silico Studies DOI

Sheetal B. Karmur,

Monil P. Dholariya, Anil S. Patel

et al.

ChemistrySelect, Journal Year: 2024, Volume and Issue: 9(39)

Published: Oct. 1, 2024

Abstract Recently, molecular hybridization strategy has paved a way to develop novel lead compounds for the α‐amylase targeted antidiabetic therapy. In this study, we disclosed series of new hybrids thiazolidine‐2,4‐diones with 2‐chloroquinoline‐3‐yl moiety as potential agents. The structures all synthesized ( 15a–n ) were confirmed by spectroscopic studies (FT‐IR, ESI‐MS, 1 H, 13 C NMR, and elemental analysis). When in vitro evaluation these agents was carried out dose‐dependent manner, it revealed that several 15f– h , 15j, 15n endowed significant activities exhibited more than 50% inhibition at dose 50 µg/mL. Particularly, hybrid found be potent acarbose 95% IC 5.00 ± 0.18 µM under given conditions. Further, demonstrated bearing 2‐chloroquinolinyl thiazolidin‐2,4‐dione scaffolds functionalized 3‐OMe 4‐OH groups not only able effectively bind receptor site best docking score (−9.644 kcal/mol) but also possessed drug‐likenesses properties no violations Lipinski rule. Overall, study discovered 2‐chloroquinolinyl‐thiazolidine‐2,4‐diones inhibitors compound promising its further development agent.

Language: Английский

Key molecular scaffolds in the development of clinically viable α-amylase inhibitors DOI
Rahul Pratap Singh, Jayant Sindhu,

Devender Singh

et al.

Future Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 17(3), P. 347 - 362

Published: Jan. 21, 2025

The escalating cases of type II diabetes combined with adverse side effects current antidiabetic drugs spurred the advancement innovative approaches for management postprandial glucose levels. α-Amylase is an endoamylase responsible breakdown internal α-1,4-glycosidic linkages in dietary starch, producing oligosaccharides. Subsequently, α-glucosidase degraded these oligosaccharides to monosaccharides, which are absorbed into bloodstream and become available body. inhibitors α-amylase reduced digestibility carbohydrates accompanied by delayed absorption, leading decreased blood levels after meals thus, inhibition enzyme seems be a crucial strategy improving overall glycemic control diabetic patients. present review article emphasizes therapeutic promise recently discovered potential inhibitors, highlighting their vitro, silico vivo profiles. Ultimately, we addressed contemporary challenges routes ahead search safe reliable clinical use, summarizing most recent research field.

Language: Английский

Citations

0
Synthesis of 2-Ethylhexyl 5-Bromothiophene-2-Carboxylates; Antibacterial Activities against Salmonella Typhi, Validation via Docking Studies, Pharmacokinetics, and Structural Features Determination through DFT DOI Creative Commons

Waseem Nazeer,

Muhammad Usman Qamar, Nasır Rasool

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(13), P. 3005 - 3005

Published: June 25, 2024

A new class of thiophene-based molecules 5-bromothiophene-2-carboxylic acid (1) have been synthesized in current research work. All analogs 4A–4G were with optimized conditions by coupling reactions 2-ethylhexyl 5-bromothiophene-2-carboxylate (3) various arylboronic acids. The results indicated that the majority compounds showed promising effective vitro antibacterial activity. Herein, 2-ethylhexyl-5-(p-tolyl)thiophene-2-carboxylate (4F), particular among analogs, outstanding action (MIC value 3.125 mg/mL) against XDR Salmonella Typhi compared to ciprofloxacin and ceftriaxone. intermolecular interaction was investigated using a molecular docking study thiophene derivatives S. Typhi. values binding affinity functionalized bacterial enzyme PDB ID: 5ztj. Therefore, 4F appears be agent highest potential value. Density functional theory (DFT) calculations executed examine electronic, structural, spectroscopic features newly 4A–4G.

Language: Английский

Citations

1
Synthesis of novel tetrahydrobenzo[b]thiophene-3-carbonitrile (THBTC)-based heterocycles: Structural insights, reactivity profiles, and in-silico bioactivity studies DOI
Jihad Sebhaoui,

Sajda Ashraf,

Shazia Iqbal

et al.

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: unknown, P. 141110 - 141110

Published: Dec. 1, 2024

Language: Английский

Citations

1
Indole–thiazolidinedione–triazole hybrids: synthesis, molecular docking, absorption, distribution, metabolism and excretion (ADME) profiling, and biological evaluation as α-amylase inhibitors DOI
Monil P. Dholariya, Anil S. Patel

Chemistry Letters, Journal Year: 2024, Volume and Issue: 53(8)

Published: July 31, 2024

Abstract A novel series of hybrid indole–thiazolidinedione–triazole derivatives (6a-l) were synthesized and assessed for their in vitro inhibitory activity against porcine pancreatic α-amylase. The synthetic procedure consists 3 steps. crucial step this process involves the generation target molecules using a Cu(I)-catalyzed azide–alkyne cycloaddition reaction. α-amylase inhibition IC50 value targeted compounds ranged from 0.51 ± 0.02 to 7.99 0.28 μM as compared with 0.68 acarbose standard drug. Using Autodock technique, all 6a-l subjected molecular docking investigations (PDB ID: 1OSE). Moreover, it was discovered that docked had excellent binding affinities −10.1 −10.8 kcal/mol −7.9 kcal/mol. Additionally, comprehensive analysis physicochemical pharmacokinetic properties associated absorption, distribution, metabolism excretion (ADME) conducted compounds.

Language: Английский

Citations

0
2‐Chloroquinolinyl‐thiazolidine‐2,4‐dione Hybrids as Potential α‐Amylase Inhibitors: Synthesis, Biological Evaluations, and In Silico Studies DOI

Sheetal B. Karmur,

Monil P. Dholariya, Anil S. Patel

et al.

ChemistrySelect, Journal Year: 2024, Volume and Issue: 9(39)

Published: Oct. 1, 2024

Abstract Recently, molecular hybridization strategy has paved a way to develop novel lead compounds for the α‐amylase targeted antidiabetic therapy. In this study, we disclosed series of new hybrids thiazolidine‐2,4‐diones with 2‐chloroquinoline‐3‐yl moiety as potential agents. The structures all synthesized ( 15a–n ) were confirmed by spectroscopic studies (FT‐IR, ESI‐MS, 1 H, 13 C NMR, and elemental analysis). When in vitro evaluation these agents was carried out dose‐dependent manner, it revealed that several 15f– h , 15j, 15n endowed significant activities exhibited more than 50% inhibition at dose 50 µg/mL. Particularly, hybrid found be potent acarbose 95% IC 5.00 ± 0.18 µM under given conditions. Further, demonstrated bearing 2‐chloroquinolinyl thiazolidin‐2,4‐dione scaffolds functionalized 3‐OMe 4‐OH groups not only able effectively bind receptor site best docking score (−9.644 kcal/mol) but also possessed drug‐likenesses properties no violations Lipinski rule. Overall, study discovered 2‐chloroquinolinyl‐thiazolidine‐2,4‐diones inhibitors compound promising its further development agent.

Language: Английский

Citations

0