Synthesis, characterization, and biocomputational assessment of the novel 3-hydroxy-4-(phenyl(pyridin-2-ylamino) methyl)-2-naphthoic acid derivatives as potential dual inhibitors of α-glucosidase and α-amylase enzymes

Shadakshari, A.J.; Kumara, T.H. Suresha; Kumar, Naveen; Chandra, Sourav; Kumar, Kuldeep; Ramu, Ramith

doi:10.1016/j.rechem.2022.100745

Cited by 3 publications

(5 citation statements)

References 25 publications

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“…(2022) and Shadakshari et al . (2023) was employed for conducting molecular docking and MD simulations. In brief, molecular docking was performed using the Autodock Vina software (https://vina.scripps.edu/), while MD simulations were conducted using GROMACS 19.5 Package (https://manual.gromacs.org/) based on the outcomes of the former.…”

Section: Methodsmentioning

confidence: 99%

Exploring antioxidant activities and inhibitory effects against α‐amylase and α‐glucosidase of Elaeocarpus braceanus fruits: insights into mechanisms by molecular docking and molecular dynamics

Li,

Zhang,

Liu

et al. 2023

Int J of Food Sci Tech

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SummaryThe present work investigated the antioxidant activity and inhibitory effects towards α‐amylase and α‐glucosidase of phenolic compounds in Elaeocarpus braceanus fruits and clarified their possible mechanisms based on molecular docking and dynamic analysis. A total of 12 phenolic compounds were identified and quantified in the extracts of E. braceanus fruits using UHPLC‐ESI‐HRMS/MS. The TPC and TFC were 229.18 ± 5.76 mg GAE/g and 144.85 ± 1.17 mg RE/g, respectively. In vitro analyses, E. braceanus fruits extracts exhibited good antioxidant activities and demonstrated strong inhibitory effects towards α‐amylase and α‐glucosidase. Molecular docking and molecular dynamics results showed that quercetin and myricetin can stably form hydrogen bonds and van der Waals forces with the active amino acid residues of α‐amylase and α‐glucosidase, and thereby inhibiting their enzymatic activities. The findings might provide a good potential natural resource for improving oxidative stress damage and controlling blood glucose in diabetes.

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Section: Methodsmentioning

confidence: 99%

Exploring antioxidant activities and inhibitory effects against α‐amylase and α‐glucosidase of Elaeocarpus braceanus fruits: insights into mechanisms by molecular docking and molecular dynamics

Li,

Zhang,

Liu

et al. 2023

Int J of Food Sci Tech

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“…Using the GA-MLR approach, this study produced a number of molecular models with descriptors in the range of (4)(5)(6). The best model was chosen based on its statistical characteristics, which indicate the robustness, strength, and consistency of the generated model.…”

Section: Qsar Model Analysis and Validation According To The Oecd Pri...mentioning

confidence: 99%

“…The dual inhibition of α-glucosidase and α-amylase enzymes is the most desired strategy for combating the permanent effects produced by type 2 diabetes [ 6 ]. α-glucosidase is one of the main enzymes that breaks down carbohydrates, and it is found in the brush borders of the intestine and helps break down complex oligosaccharides into simple monosaccharides [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Integrative Approach for Designing Novel Triazole Derivatives as α-Glucosidase Inhibitors: QSAR, Molecular Docking, ADMET, and Molecular Dynamics Investigations

Abchir,

Khedraoui,

Nour

et al. 2024

Pharmaceuticals

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In response to the increasing prevalence of diabetes mellitus and the limitations associated with the current treatments, there is a growing need to develop novel medications for this disease. This study is focused on creating new compounds that exhibit a strong inhibition of alpha-glucosidase, which is a pivotal enzyme in diabetes control. A set of 33 triazole derivatives underwent an extensive QSAR analysis, aiming to identify the key factors influencing their inhibitory activity against α-glucosidase. Using the multiple linear regression (MLR) model, seven promising compounds were designed as potential drugs. Molecular docking and dynamics simulations were employed to shed light on the mode of interaction between the ligands and the target, and the stability of the obtained complexes. Furthermore, the pharmacokinetic properties of the designed compounds were assessed to predict their behavior in the human body. The binding free energy was also calculated using MMGBSA method and revealed favorable thermodynamic properties. The results highlighted three novel compounds with high biological activity, strong binding affinity to the target enzyme, and suitability for oral administration. These results offer interesting prospects for the development of effective and well-tolerated medications against diabetes mellitus.

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“…To get a better insight into the interactions between the ligands, the evolution in time of the predicted complexes compounds with VEGFR2 was studied in a molecular dynamics study using GROMACS 2023 for 100 ns using a CHARMM36 force field on a machine running Debian 11 with CUDA 12 for operating an NVIDIA RTX 3060 GPU [47][48][49][50][51]. For each constructed complex, the top binding conformation of each ligand and their parametrization was performed using CgenFF [47].…”

Section: Molecular Dynamics Studiesmentioning

confidence: 99%

“…This in silico technique was used to determine the motions of the molecules in a sampled system during simulation, in conditions as close as possible to reality [61]. As the computing power of computers increased in recent years, this technique began to be routinely used to validate molecular docking results to evaluate the degree of stability of the ligand in the target protein [50].…”

Section: Molecular Dynamics Studiesmentioning

confidence: 99%

Discovery of A Novel Series of Quinazoline–Thiazole Hybrids as Potential Antiproliferative and Anti-Angiogenic Agents

Șandor,

Fizeșan,

Ionuț

et al. 2024

Biomolecules

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Considering the pivotal role of angiogenesis in solid tumor progression, we developed a novel series of quinazoline–thiazole hybrids (SA01–SA07) as antiproliferative and anti-angiogenic agents. Four out of the seven compounds displayed superior antiproliferative activity (IC50 =1.83-4.24 µM) on HepG2 cells compared to sorafenib (IC50 = 6.28 µM). The affinity towards the VEGFR2 kinase domain was assessed through in silico prediction by molecular docking, molecular dynamics studies, and MM-PBSA. The series displayed a high degree of similarity to sorafenib regarding the binding pose within the active site of VEGFR2, with a different orientation of the 4-substituted-thiazole moieties in the allosteric pocket. Molecular dynamics and MM-PBSA evaluations identified SA05 as the hybrid forming the most stable complex with VEGFR2 compared to sorafenib. The impact of the compounds on vascular cell proliferation was assessed on EA.hy926 cells. Six compounds (SA01–SA05, SA07) displayed superior anti-proliferative activity (IC50 = 0.79–5.85 µM) compared to sorafenib (IC50 = 6.62 µM). The toxicity was evaluated on BJ cells. Further studies of the anti-angiogenic effect of the most promising compounds, SA04 and SA05, through the assessment of impact on EA.hy296 motility using a wound healing assay and in ovo potential in a CAM assay compared to sorafenib, led to the confirmation of the anti-angiogenic potential.

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Synthesis, characterization, and biocomputational assessment of the novel 3-hydroxy-4-(phenyl(pyridin-2-ylamino) methyl)-2-naphthoic acid derivatives as potential dual inhibitors of α-glucosidase and α-amylase enzymes

Cited by 3 publications

References 25 publications

Exploring antioxidant activities and inhibitory effects against α‐amylase and α‐glucosidase of Elaeocarpus braceanus fruits: insights into mechanisms by molecular docking and molecular dynamics

Exploring antioxidant activities and inhibitory effects against α‐amylase and α‐glucosidase of Elaeocarpus braceanus fruits: insights into mechanisms by molecular docking and molecular dynamics

Integrative Approach for Designing Novel Triazole Derivatives as α-Glucosidase Inhibitors: QSAR, Molecular Docking, ADMET, and Molecular Dynamics Investigations

Discovery of A Novel Series of Quinazoline–Thiazole Hybrids as Potential Antiproliferative and Anti-Angiogenic Agents

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