A Combined Experimental and Computational Study of Novel Benzotriazinone Carboxamides as Alpha-Glucosidase Inhibitors DOI Creative Commons
Zunera Khalid, Syed Salman Shafqat, Hafiz Adnan Ahmad

et al.

Molecules, Journal Year: 2023, Volume and Issue: 28(18), P. 6623 - 6623

Published: Sept. 14, 2023

Diabetes is a chronic metabolic disorder of the endocrine system characterized by persistent hyperglycemia appears due to deficiency or ineffective use insulin. The glucose level diabetic patients increases after every meal and medically recommended drugs are used control hyperglycemia. Alpha-glucosidase inhibitors as antidiabetic medicine delay hydrolysis complex carbohydrates. Acarbose, miglitol, voglibose commercial but suffer side effects flatulence, bloating, diarrhea, loss hunger. To explore new drug, series benzotriazinone carboxamides was synthesized their alpha-glucosidase inhibition potentials were measured using in vitro experiments. compounds 14k 14l found be strong compared standard drug acarbose with IC50 values 27.13 ± 0.12 32.14 0.11 μM, respectively. In silico study carried out molecular docking identify type interactions developed between these enzyme sites. Both potent exhibited effective scores making selected amino acid residues. Chemical hardness orbital energy gap investigated DFT studies results depicted affinity towards biological molecules. All computational findings good agreement results.

Language: Английский

Pyrazoline Derivatives as Promising MAO-A Targeting Antidepressants: An Update DOI
Diksha Choudhary, Rajwinder Kaur, Thakur Gurjeet Singh

et al.

Current Topics in Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 24(5), P. 401 - 415

Published: Feb. 1, 2024

Abstract: Depression is one of the key conditions addressed by Mental Health Gap Action Programme (mhGAP) WHO that can lead to self-harm and suicide. associated with low levels neurotransmitters, which eventually play a role in progression development mental illness. The nitrogen-containing heterocyclic compounds exhibit most prominent pharmacological profile as antidepressants. Pyrazoline, dihydro derivative pyrazole, well-known five-membered moiety exhibits broad spectrum biological activities. Many researchers have reported pyrazoline scaffold-containing molecules potential antidepressant agents selectivity for monoamine oxidase enzyme (MAO) isoforms. Several studies indicated better affinity pyrazoline-based (monoamine inhibitors) MAOIs. In this review, we focused on recent advancements (2019-2023) pyrazoline-containing derivatives exhibiting promising inhibition MAO-A treat depression. This review provides structural insights along their SAR analysis, silico exploration binding interactions between enzyme, clinical trial status various drug against in-silico potent at active site MAOA will provide further into new inhibitors treatment

Language: Английский

Citations

4
Novel Aromatic Heterocycles for Dual MAO A and B Inhibitors: A Promising Strategy for Parkinson's Disease Treatment DOI Open Access

Swati,

Amir Raza, Bhupendra Singh

et al.

ChemistrySelect, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 1, 2025

Abstract Recent advancements in the synthesis of aromatic heterocycles have shown promise inhibition monoamine oxidase (MAO) A and B enzymes implicated pathophysiology Parkinson's disease (PD). These heterocyclic compounds are particular interest due to their structural diversity significant pharmacological potential.This review discusses various strategies for enhancing MAO inhibitory activity, emphasizing positional modifications. Notable progress includes development thiazole‐based imidazole‐based with detailed exploration synthetic methodologies structure–activity relationships. demonstrated potential targeting metabolism neurotransmitters, particularly dopamine, which is crucial managing PD symptoms.The offers a promising pathway developing novel therapeutics disease. The these compounds, combined ability modulate neurotransmitter levels, present hopeful avenue more effective management. However, further research, including structure‐based design vivo validation, essential fully realize therapeutic efficacy improve treatment outcomes

Language: Английский

Citations

0
Monoamine Oxidase Inhibitors in Toxic Models of Parkinsonism DOI Open Access
О.А. Бунеева, A. E. Medvedev

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1248 - 1248

Published: Jan. 31, 2025

Monoamine oxidase inhibitors are widely used for the symptomatic treatment of Parkinson's disease (PD). They demonstrate antiparkinsonian activity in different toxin-based models induced by 6-hydroxydopamine, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and pesticides (rotenone paraquat). In some models, such as MPTP-induced PD, MAO prevent formation neurotoxin MPP+ from protoxin MPTP. Regardless toxin's nature, potent dopamine loss reduction, hydrogen peroxide, peroxide signaling, accumulation peroxide-derived reactive oxygen species responsible development oxidative stress. It becomes increasingly clear that metabolites (e.g., rasagiline metabolite 1-R-aminoindan) possess their own bio-pharmacological activities unrelated to parent compound. addition, various exhibit multitarget action, which MAO-independent effects prevail. This opens new prospects novel therapeutics based on simultaneous actions several prospective targets therapy PD.

Language: Английский

Citations

0
In-silico molecular modelling studies of some camphor imine based compounds as anti-influenza A (H1N1) pdm09 virus agents DOI
Mustapha Abdullahi,

Adamu Uzairu,

Gideon Adamu Shallangwa

et al.

Journal of Biomolecular Structure and Dynamics, Journal Year: 2023, Volume and Issue: 42(4), P. 2013 - 2033

Published: May 11, 2023

The advent of influenza A (H1N1) drug-resistant strains led to the search quest for more potent inhibitors virus, especially in this devastating COVID-19 pandemic era. Hence, present research utilized some molecular modelling strategies unveil new camphor imine-based compounds as anti-influenza pdm09 agents. 2D-QSAR results revealed GFA-MLR (R2train = 0.9158, Q2=0.8475) and GFA-ANN 0.9264, Q2=0.9238) models activity prediction which have passed QSAR model acceptability thresholds. from 3D-QSAR studies also CoMFA =0.977, Q2=0.509) CoMSIA_S =0.976, Q2=0.527) predictions. Based on notable information derived 2D-QSAR, 3D-QSAR, docking analysis, ten (10) (22a-22j) were designed using most active compound 22 template. Furthermore, high predicted binding scores 22j further justified by reactive sites shown electrostatic potential maps other quantum chemical calculations. MD simulation site hemagglutinin (HA) receptor confirmed dynamic stability complex. Moreover, appraisals drug-likeness ADMET properties proposed showed zero violation Lipinski's criteria with good pharmacokinetic profiles. outcomes work recommend in-depth vivo in-vitro investigations validate these theoretical findings.Communicated Ramaswamy H. Sarma

Language: Английский

Citations

5
A Combined Experimental and Computational Study of Novel Benzotriazinone Carboxamides as Alpha-Glucosidase Inhibitors DOI Creative Commons
Zunera Khalid, Syed Salman Shafqat, Hafiz Adnan Ahmad

et al.

Molecules, Journal Year: 2023, Volume and Issue: 28(18), P. 6623 - 6623

Published: Sept. 14, 2023

Diabetes is a chronic metabolic disorder of the endocrine system characterized by persistent hyperglycemia appears due to deficiency or ineffective use insulin. The glucose level diabetic patients increases after every meal and medically recommended drugs are used control hyperglycemia. Alpha-glucosidase inhibitors as antidiabetic medicine delay hydrolysis complex carbohydrates. Acarbose, miglitol, voglibose commercial but suffer side effects flatulence, bloating, diarrhea, loss hunger. To explore new drug, series benzotriazinone carboxamides was synthesized their alpha-glucosidase inhibition potentials were measured using in vitro experiments. compounds 14k 14l found be strong compared standard drug acarbose with IC50 values 27.13 ± 0.12 32.14 0.11 μM, respectively. In silico study carried out molecular docking identify type interactions developed between these enzyme sites. Both potent exhibited effective scores making selected amino acid residues. Chemical hardness orbital energy gap investigated DFT studies results depicted affinity towards biological molecules. All computational findings good agreement results.

Language: Английский

Citations

4