Synthesis, in vitro potency of inhibition, enzyme kinetics and in silico studies of quinoline-based α-glucosidase inhibitors

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Янв. 4, 2024

Abstract Diabetes mellitus is a multifactorial global health disorder that rising at an alarming rate. One effective therapeutic approach for controlling hyperglycemia associated with type-2 diabetes to target α-glucosidase, which catalyzes starch hydrolysis in the intestine. In attempt find potential α-glucosidase inhibitors, series of twenty new quinoline linked benzothiazole hybrids ( 8a–t ) were synthesized good yields from suitable reaction procedures and their chemical structures analyzed by 1 HNMR, 13 CNMR, IR, ESI–MS analysis. The derivatives further screened activity against α-glucosidase. Among them, compounds 8b , 8h 8n 8o exhibited remarkable inhibitory IC 50 values ranging 38.2 ± 0.3 79.9 1.2 µM compared standard drug acarbose (IC = 750.0 2.0 µM). Enzyme kinetic studies most active compound indicated non-competitive inhibition K i value µM. Moreover, homology modeling, molecular docking dynamics simulation conducted reveal key interactions between targeted enzyme. These results are complementary experimental observations. order predict druggability novel derivatives, pharmacokinetic properties also applied. findings could be useful design development inhibitors.

Язык: Английский

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Discovery of triazole tethered thymol/carvacrol-coumarin hybrids as new class of α-glucosidase inhibitors with potent in vivo antihyperglycemic activities

European Journal of Medicinal Chemistry, Год журнала: 2023, Номер 263, С. 115948 - 115948

Опубликована: Ноя. 15, 2023

Язык: Английский

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Isatin-semicarbazone linked acetamide 1,2,3-triazole hybrids: Synthesis, antimicrobial evaluation and docking simulations

Journal of Molecular Structure, Год журнала: 2023, Номер 1287, С. 135660 - 135660

Опубликована: Апрель 25, 2023

Язык: Английский

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An insight on medicinal attributes of 1,2,3‐ and 1,2,4‐triazole derivatives as alpha-amylase and alpha-glucosidase inhibitors

Molecular Diversity, Год журнала: 2023, Номер unknown

Опубликована: Сен. 21, 2023

Язык: Английский

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Novel coumarin-thiazolidine-2,4-dione hybrids as potential α-glucosidase inhibitors: Synthesis and bioactivity evaluation

Journal of Molecular Structure, Год журнала: 2024, Номер unknown, С. 140481 - 140481

Опубликована: Окт. 1, 2024

Язык: Английский

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Recent Developments in 1,2,3‐Triazole Based α‐Glucosidase Inhibitors: Design Strategies, Structure‐Activity Relationship and Mechanistic Insights

Chemistry & Biodiversity, Год журнала: 2024, Номер 21(9)

Опубликована: Июль 2, 2024

Diabetes mellitus is a chronic and most prevalent metabolic disorder affecting 422 million the people worldwide causing life-threatening associated conditions including disorders of kidney, heart, nervous system as well leg amputation retinopathy. Steadily rising cases from last few decades suggest failure currently available drugs in containment this disease. α-Glucosidase potential target for effectively tackling disease attracting significant interest medicinal chemists around globe. Besides having set side effects, α-glucosidase inhibitors (carbohydrate mimics) offer better tolerability, safety, synergistic pharmacological outcomes with other antidiabetic therefore have working extensively over three developing alternative inhibitors. The 1,2,3-Triazole nucleus energetically used by various research groups globe development posing it an optimum scaffold field drug development. This review systematic analysis developed employing 1,2,3-triazole special focus on design strategies, structure-activity relationships, mechanism inhibitory effect. article will act lantern potent, safer, effective desired properties improved therapeutic efficacy.

Язык: Английский

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Design and synthesis of new coumarin-1,2,3-triazole hybrids as new antidiabetic agents: In vitro α-amylase, α-glucosidase inhibition, anti-inflammatory, and docking study

European Journal of Chemistry, Год журнала: 2024, Номер 15(3), С. 205 - 219

Опубликована: Сен. 30, 2024

The current study focuses on the synthesis of coumarin-triazole hybrids (7i-t) starting from 4-hydroxy benzaldehyde or 4-hydroxyacetophenone (1a-b) and propargyl bromide. On other hand, coumarin derivatives (5c-h) were prepared by Pechmann cyclization treated with sodium azide to give corresponding 3-azido methyl coumarins (6c-h). Finally, 1,3-dipolar cycloaddition between compounds 6c-h terminal alkyne 2a-b produces utilizing click chemistry approaches that are high yielding, wide in scope simple perform. structural proofs newly synthesized proved various spectroscopic techniques, including IR, 1H NMR, 13C LC-MS. new triazole explored for their antihyperglycemic potential therefore evaluated α-glucosidase α-amylase inhibitory activities along anti-inflammatory. results suggest among series, compound 7l showed excellent activity an IC50 value 0.67±0.014 mg/mL 0.72±0.012 α-amylase, while 7o promising anti-inflammatory 0.54±0.003 mg/mL. To support above findings, molecular docking studies performed, which confirmed interaction molecules 7i-t effective binding energy -9.0 -10.6 kcal/mol at active site enzyme human pancreatic (PDB ID: 1B2Y). Therefore, these scaffolds have function as lead candidates antidiabetic activities.

Язык: Английский

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Thiazolidinedione–Triazole Conjugates: Design, Synthesis and Probing of the α-Amylase Inhibitory Potential

Future Medicinal Chemistry, Год журнала: 2023, Номер 15(14), С. 1273 - 1294

Опубликована: Июль 1, 2023

Aim: The primary objective of this investigation was the synthesis, spectral interpretation and evaluation α-amylase inhibition rationally designed thiazolidinedione-triazole conjugates (7a-7aa). Materials & methods: compounds were synthesized by stirring a mixture thiazolidine-2,4-dione, propargyl bromide, cinnamaldehyde azide derivatives in polyethylene glycol-400. inhibitory activity examined integrating vitro silico studies. Results: investigated exhibited promising activity, with IC50 values ranging between 0.028 0.088 μmol ml-1. Various computational approaches employed to get detailed information about mechanism. Conclusion: conjugate 7p, = ml-1, identified as best hit for inhibiting α-amylase.

Язык: Английский

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Multi-target directed ligands inspired natural products as an effective approach for the treatment of complex chronic health disorders

Bioorganic Chemistry, Год журнала: 2024, Номер 154, С. 108075 - 108075

Опубликована: Дек. 17, 2024

Язык: Английский

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In vitro exploration of Hypsizygus ulmarius (Bull.) mushroom fruiting bodies: Potential antidiabetic and anti-inflammatory agent

Open Chemistry, Год журнала: 2023, Номер 21(1)

Опубликована: Янв. 1, 2023

Abstract The growing interest in exploring mushrooms and their bioactive components as potential therapies for diabetes inflammatory conditions has prompted our investigation. In this study, we examined the methanolic extract, well petroleum ether ethyl acetate fractions, derived from fruiting bodies of Hypsizygus ulmarius assessed vitro anti-inflammatory anti-diabetic effects. inhibition salivary α-amylase, sucrase, α-glucosidase enzymes by extract its fractions was used to measure level antidiabetic activity. Further, inhibitory effects lipoxygenase (LOX), cyclooxygenase (COX), myeloperoxidase (MPO) were tested assess efficacy fractions. fraction containing been demonstrated have highest effect, exhibiting IC 50 values 44.93, 27.70, 44.75 μg/ml enzymes, respectively. Moreover, revealed greatest action, with 25.67 LOX, 34.04 COX, 38.71 MPO.

Язык: Английский

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