Mechanistic inhibition of non-enzymatic glycation and aldose reductase activity by naringenin: Binding, enzyme kinetics and molecular docking analysis

Khan, Mohd Shahnawaz; Qais, Faizan Abul; Rehman, Tabish; Ismail, M.H.; Alokail, Majed S.; Altwaijry, Nojood; Alafaleq, Nouf Omar; Alajmi, Mohamed F.; Salem, Nusaibah; Alqhatani, Rawiah

doi:10.1016/j.ijbiomac.2020.04.226

Cited by 39 publications

(31 citation statements)

References 56 publications

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“…2.6. Detection of Early Glycation (Amadori) Products: Quantification of Fructosamine NBT assay was used to determine fructosamine content; the previously used protocol was used [42]. Briefly, 0.5 mM NBT was mixed with samples (0.5 mg/mL) and incubated in 100 mM sodium carbonate buffer of pH 10.4.…”

Section: Determination Of Advanced Glycation End-products (Ages)mentioning

confidence: 99%

Binding Studies of Caffeic and p-Coumaric Acid with α-Amylase: Multispectroscopic and Computational Approaches Deciphering the Effect on Advanced Glycation End Products (AGEs)

et al. 2022

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Alpha-amylase (α-amylase) is a key player in the management of diabetes and its related complications. This study was intended to have an insight into the binding of caffeic acid and coumaric acid with α-amylase and analyze the effect of these compounds on the formation of advanced glycation end-products (AGEs). Fluorescence quenching studies suggested that both the compounds showed an appreciable binding affinity towards α-amylase. The evaluation of thermodynamic parameters (ΔH and ΔS) suggested that the α-amylase-caffeic/coumaric acid complex formation is driven by van der Waals force and hydrogen bonding, and thus complexation process is seemingly specific. Moreover, glycation and oxidation studies were also performed to explore the multitarget to manage diabetes complications. Caffeic and coumaric acid both inhibited fructosamine content and AGE fluorescence, suggesting their role in the inhibition of early and advanced glycation end-products (AGEs). However, the glycation inhibitory potential of caffeic acid was more in comparison to p-coumaric acid. This high antiglycative potential can be attributed to its additional –OH group and high antioxidant activity. There was a significant recovery of 84.5% in free thiol groups in the presence of caffeic acid, while coumaric attenuated the slow recovery of 29.4% of thiol groups. In vitro studies were further entrenched by in silico studies. Molecular docking studies revealed that caffeic acid formed six hydrogen bonds (Trp 59, Gln 63, Arg 195, Arg 195, Asp 197 and Asp 197) while coumaric acid formed four H-bonds with Trp 59, Gln 63, Arg 195 and Asp 300. Our studies highlighted the role of hydrogen bonding, and the ligands such as caffeic or coumaric acid could be exploited to design antidiabetic drugs.

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Section: Determination Of Advanced Glycation End-products (Ages)mentioning

confidence: 99%

Binding Studies of Caffeic and p-Coumaric Acid with α-Amylase: Multispectroscopic and Computational Approaches Deciphering the Effect on Advanced Glycation End Products (AGEs)

et al. 2022

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“…During molecular dynamics simulation, the variation in the conformation of amino acid residues is monitored by estimating root mean square fluctuation (RMSF) over the simulation time to gain an insight into the protein's overall conformational stability [ 48 ]. This study monitored the RMSFs of BACE-1 and γ-secretase in free forms and their complex structures with 6Z5 ( Figure 4(C,D) ).…”

Section: Resultsmentioning

confidence: 99%

Concatenation of molecular docking and molecular simulation of BACE-1, γ-secretase targeted ligands: in pursuit of Alzheimer’s treatment

et al. 2021

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Introduction Alzheimer's disease (AD), the most predominant cause of dementia, has evolved tremendously with an escalating frequency, mainly affecting the elderly population. An effective means of delaying, preventing, or treating AD is yet to be achieved. The failure rate of dementia drug trials has been relatively higher than in other disease-related clinical trials. Hence, multi-targeted therapeutic approaches are gaining attention in pharmacological developments. Aims As an extension of our earlier reports, we have performed docking and molecular dynamic (MD) simulation studies for the same 13 potential ligands against beta-site APP cleaving enzyme 1 (BACE-1) and γ-secretase as a therapeutic target for AD. The In-silico screening of these ligands as potential inhibitors of BACE-1 and γ- secretase was performed using AutoDock enabled PyRx v-0.8. The protein-ligand interactions were analyzed in Discovery Studio 2020 (BIOVIA). The stability of the most promising ligand against BACE-1 and γ- secretase was evaluated by MD simulation using Desmond-2018 (Schrodinger, LLC, NY, USA). Results The computational screening revealed that the docking energy values for each of the ligands against both the target enzymes were in the range of −7.0 to −10.1 kcal/mol. Among the 13 ligands, 8 (55E, 6Z2, 6Z5, BRW, F1B, GVP, IQ6, and X37) showed binding energies of ≤−8 kcal/mol against BACE-1 and γ-secretase. For the selected enzyme targets, BACE-1 and γ-secretase, 6Z5 displayed the lowest binding energy of −10.1 and −9.8 kcal/mol, respectively. The MD simulation study confirmed the stability of BACE-6Z5 and γ-secretase-6Z5 complexes and highlighted the formation of a stable complex between 6Z5 and target enzymes. Conclusion The virtual screening, molecular docking, and molecular dynamics simulation studies revealed the potential of these multi-enzyme targeted ligands. Among the studied ligands, 6Z5 seems to have the best binding potential and forms a stable complex with BACE-1 and γ-secretase. We recommend the synthesis of 6Z5 for future in-vitro and in-vivo studies.

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“…The results were analyzed in Discovery Studio2.5 (Accelrys). The binding affinity ( K d ) of the ligand towards protein was calculated from its binding energy (Δ G ) using the relation (Khan et al, 2020 ; Rabbani et al, 2018 ): where R and T are the universal gas constant and temperature, respectively.…”

Section: Methodsmentioning

confidence: 99%

Celecoxib, Glipizide, Lapatinib, and Sitagliptin as potential suspects of aggravating SARS-CoV-2 (COVID-19) infection: a computational approach

Alajmi

Rehman

Hussain

2021

Journal of Biomolecular Structure and Dynamics

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Mechanistic inhibition of non-enzymatic glycation and aldose reductase activity by naringenin: Binding, enzyme kinetics and molecular docking analysis

Cited by 39 publications

References 56 publications

Binding Studies of Caffeic and p-Coumaric Acid with α-Amylase: Multispectroscopic and Computational Approaches Deciphering the Effect on Advanced Glycation End Products (AGEs)

Binding Studies of Caffeic and p-Coumaric Acid with α-Amylase: Multispectroscopic and Computational Approaches Deciphering the Effect on Advanced Glycation End Products (AGEs)

Concatenation of molecular docking and molecular simulation of BACE-1, γ-secretase targeted ligands: in pursuit of Alzheimer’s treatment

Celecoxib, Glipizide, Lapatinib, and Sitagliptin as potential suspects of aggravating SARS-CoV-2 (COVID-19) infection: a computational approach

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