scholarly journals Synthesis, molecular docking, and antiepileptic activity of novel phthalimide derivatives bearing amino acid conjugated anilines

2019 ◽  
Vol 14 (6) ◽  
pp. 534
Author(s):  
Massoud Amanlou ◽  
Azar Asadollahi ◽  
Mehdi Asadi ◽  
FaezehSadat Hosseini ◽  
Zeinab Ekhtiari ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Amino Acid ◽  
Antiepileptic Activity

Molecular Docking Analysis of Flavonoid Compounds with Matrix Metalloproteinase-8 for the Identification of Potential Effective Inhibitors

2020 ◽  
Vol 17 ◽  
Author(s):  
Amir Taherkhani ◽  
Athena Orangi ◽  
Shirin Moradkhani ◽  
Zahra Khamverdi
Keyword(s):  
Amino Acids ◽  
Molecular Docking ◽  
Amino Acid ◽  
Matrix Metalloproteinase ◽  
Ligand Binding ◽  
Chronic Inflammation ◽  
Cancer Progression ◽  
Dimensional Structure ◽  
Control Test ◽  
Therapeutic Procedures

Background: Matrix metalloproteinase-8 (MMP-8) participates in degradation of different types of collagens in the extracellular matrix and basement membrane. Up-regulation of the MMP-8 has been demonstrated in many of disorders including cancer development, tooth caries, periodontal/peri-implant soft and hard tissue degeneration, and acute/chronic inflammation. Therefore, MMP-8 has become an encouraging target for therapeutic procedures for scientists. We carried out molecular docking approach to study the binding affinity of 29 flavonoids, as drug candidates, with the MMP-8. Pharmacokinetic and toxicological properties of the compounds were also studied. Moreover, it was attempted to identify the most important amino acids participating in ligand binding based on degree of each of the amino acids in the ligand-amino acid interaction network for MMP-8. Methods: Three-dimensional structure of the protein was gained from the RCSB database (PDB ID: 4QKZ). AutoDock version 4.0 and Cytoscape 3.7.2 were used for molecular docking and network analysis, respectively. Notably, the inhibitor of the protein in the crystalline structure of the 4QKZ was considered as a control test. Pharmacokinetic and toxicological features of compounds were predicted using bioinformatic web tools. Post-docking analyses were performed using BIOVIA Discovery Studio Visualizer version 19.1.0.18287. Results and Discussions: According to results, 24 of the studied compounds considered to be top potential inhibitors for MMP-8 based on their salient estimated free energy of binding and inhibition constant as compared with the control test: Apigenin-7-glucoside, nicotiflorin, luteolin, glabridin, taxifolin, apigenin, licochalcone A, quercetin, isorhamnetin, myricetin, herbacetin, kaemferol, epicatechin, chrysin, amentoflavone, rutin, orientin, epiafzelechin, quercetin-3-rhamnoside, formononetin, isoliquiritigenin, vitexin, catechine, isoquercitrin. Moreover, His-197 was found to be the most important amino acid involved in the ligand binding for the enzyme. Conclusion: The results of the current study could be used in the prevention and therapeutic procedures of a number of disorders such as cancer progression and invasion, oral diseases, and acute/chronic inflammation. Although, in vitro and in vivo tests are inevitable in the future.

scholarly journals In Silico Prediction, Molecular Docking and Dynamics Studies of Steroidal Alkaloids of Holarrhena pubescens Wall. ex G. Don to Guanylyl Cyclase C: Implications in Designing of Novel Antidiarrheal Therapeutic Strategies

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4147
Author(s):  
Neha Gupta ◽  
Saurav Kumar Choudhary ◽  
Neeta Bhagat ◽  
Muthusamy Karthikeyan ◽  
Archana Chaturvedi
Keyword(s):  
Molecular Docking ◽  
Amino Acid ◽  
Guanylyl Cyclase ◽  
Extracellular Domain ◽  
Enterotoxigenic Escherichia Coli ◽  
Watery Diarrhea ◽  
Guanylyl Cyclase C ◽  
Amino Acid Residues ◽  
Lead Compounds

The binding of heat stable enterotoxin (STa) secreted by enterotoxigenic Escherichia coli (ETEC) to the extracellular domain of guanylyl cyclase c (ECDGC-C) causes activation of a signaling cascade, which ultimately results in watery diarrhea. We carried out this study with the objective of finding ligands that would interfere with the binding of STa on ECDGC-C. With this view in mind, we tested the biological activity of a alkaloid rich fraction of Holarrhena pubescens against ETEC under in vitro conditions. Since this fraction showed significant antibacterial activity against ETEC, we decided to test the screen binding affinity of nine compounds of steroidal alkaloid type from Holarrhena pubescens against extracellular domain (ECD) by molecular docking and identified three compounds with significant binding energy. Molecular dynamics simulations were performed for all the three lead compounds to establish the stability of their interaction with the target protein. Pharmacokinetics and toxicity profiling of these leads demonstrated that they possessed good drug-like properties. Furthermore, the ability of these leads to inhibit the binding of STa to ECD was evaluated. This was first done by identifying amino acid residues of ECDGC-C binding to STa by protein–protein docking. The results were matched with our molecular docking results. We report here that holadysenterine, one of the lead compounds that showed a strong affinity for the amino acid residues on ECDGC-C, also binds to STa. This suggests that holadysenterine has the potential to inhibit binding of STa on ECD and can be considered for future study, involving its validation through in vitro assays and animal model studies.

Physicochemical investigations of amino acid ionic liquid based inclusion complex probed by spectral and molecular docking techniques

2019 ◽  
Vol 291 ◽  
pp. 111255 ◽  
Author(s):  
Koyeli Das ◽  
Bhaswati Sarkar ◽  
Pritam Roy ◽  
Chandana Basak ◽  
Ranadhir Chakraborty ◽  
...  
Keyword(s):  
Ionic Liquid ◽  
Molecular Docking ◽  
Amino Acid ◽  
Inclusion Complex ◽  
Amino Acid Ionic Liquid

scholarly journals Molecular Modification of Fluoroquinolone-Biodegrading Enzymes Based on Molecular Docking and Homology Modelling

2019 ◽  
Vol 16 (18) ◽  
pp. 3407 ◽  
Author(s):  
Liu ◽  
Sun ◽  
Cui ◽  
Ding
Keyword(s):  
Molecular Docking ◽  
Amino Acid ◽  
Homology Modelling ◽  
Binding Affinities ◽  
The Novel ◽  
Amino Acid Residues ◽  
Degrading Enzyme ◽  
Degrading Enzymes ◽  
Docking Method ◽  
Degradation Effect

To improve the biodegradation efficiency of fluoroquinolone antibiotics during sewage treatment, fluoroquinolone aerobic, anaerobic and facultative degrading enzymes for fluoroquinolone degradation were modified by molecular docking and homology modelling. First, amino acid residues of the binding sites of degrading enzymes for the target fluoroquinolones ciprofloxacin (CIP), norfloxacin (NOR) and ofloxacin (OFL) were analysed by the molecular docking method. The hydrophobic amino acid residues within 5 Å of the target fluoroquinolone molecules were selected as the modification sites. The hydrophobic amino acid residues at the modified sites were replaced by the hydrophilic amino acid residues, and 150 amino acid sequence modification schemes of the degrading enzymes were designed. Subsequently, a reconstruction scheme of the degrading enzyme amino acid sequence reconstruction scheme was submitted to the SWISS-MODEL server and a selected homology modelling method was used to build a new structure of the degrading enzyme. At the same time, the binding affinities between the novel degrading enzymes and the target fluoroquinolones (represented by the docking scoring function) were evaluated by the molecular docking method. It was found that the novel enzymes can simultaneously improve the binding affinities for the three target fluoroquinolones, and the degradation ability of the six modification schemes was increased by more than 50% at the same time. Among the novel enzymes, the affinity effect of the novel anaerobic enzyme (6-1) with CIP, NOR and OFL was significantly increased, with increases of 129.24%, 165.06% and 169.59%, respectively, followed by the facultative enzyme and aerobic enzyme. In addition, the designed degrading enzymes had certain selectivity for the degradation of the target quinolone. Among the novel enzymes, the binding affinities of the novel anaerobic enzyme (6-3) and CIP, the novel aerobic enzyme (3-6) and NOR, and the novel facultative enzyme (13-6) and OFL were increased by 149.71%, 178.57% and 297.12% respectively. Calculations using the Gaussian09 software revealed that the degradation reaction barrier of the novel degrading enzyme (7-1) and CIP NOR and OFL decreased by 37.65 kcal·mol−1, 6.28 kcal·mol−1 and 6.28 kcal·mol−1, respectively, which would result in efficient degradation of the target fluoroquinolone molecules. By analysing the binding affinity of the degrading enzymes before and after the modification with methanol, it was further speculated that the degradation effect of the modified aerobic degrading enzymes on organic matter was lower than that before the modification, and the increase or decrease in the degradation effect was less than 10%. The mechanism analysis found that the interaction between the modified amino acid residues of the degrading enzymes and the fluoroquinolone molecules increased. The average distance between the amino acid residues and the fluoroquinolone molecules represented a comprehensive affinity effect, and its value was positively correlated with the degradation effect of the novel degrading enzymes.

scholarly journals ACE Inhibitory Activity and Molecular Docking of Gac Seed Protein Hydrolysate Purified by HILIC and RP-HPLC

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4635
Author(s):  
Samuchaya Ngamsuk ◽  
Tzou-Chi Huang ◽  
Jue-Liang Hsu
Keyword(s):  
Liquid Chromatography ◽  
Molecular Docking ◽  
Amino Acid ◽  
Inhibitory Activity ◽  
Seed Proteins ◽  
Inhibition Mechanism ◽  
Ace Inhibitory Activity ◽  
Rp Hplc ◽  
Inhibitory Activities ◽  
Ace Inhibitory

Gac (Momordica cochinchinensis Spreng.) seed proteins (GSPs) hydrolysate was investigated for angiotensin I-converting enzyme (ACE) inhibitory activities. GSPs were hydrolyzed under simulated gastrointestinal digestion using a combination of enzymes, including pepsin, trypsin, and chymotrypsin. The screening of ACE inhibitory peptides from GSPs hydrolysate was performed using two sequential bioassay-guided fractionations, namely hydrophilic interaction liquid chromatography (HILIC) and reversed-phase high-performance liquid chromatography (RP-HPLC). Then, the peptides in the fraction with the highest ACE inhibitory activity were identified by LC-MS/MS. The flow-through (FT) fraction showed the most potent ACE inhibitory activity when HILIC fractionation was performed. This fraction was further separated using RP-HPLC, and the result indicated that fraction 8 (RP-F8) showed the highest ACE inhibitory activity. In the HILIC-FT/RP-F8 fraction, 14 peptides were identified using LC-MS/MS analysis coupled with de novo sequencing. These amino acid chains had not been recorded previously and their ACE inhibitory activities were analyzed in silico using the BIOPEP database. One fragment with the amino acid sequence of ALVY showed a significant ACE inhibitory activity (7.03 ± 0.09 µM). The Lineweaver-Burk plot indicated that ALVY is a competitive inhibitor. The inhibition mechanism of ALVY against ACE was further rationalized through the molecular docking simulation, which revealed that the ACE inhibitory activities of ALVY is due to interaction with the S1 (Ala354, Tyr523) and the S2 (His353, His513) pockets of ACE. Bibliographic survey allowed the identification of similarities between peptides reported as in gac fruit and other proteins. These results suggest that gac seed proteins hydrolysate can be used as a potential nutraceutical with inhibitory activity against ACE.

scholarly journals Screening and Characterizing Tyrosinase Inhibitors from Salvia miltiorrhiza and Carthamus tinctorius by Spectrum-Effect Relationship Analysis and Molecular Docking

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Ya-Li Wang ◽  
Guang Hu ◽  
Qian Zhang ◽  
Yu-Xiu Yang ◽  
Qiao-Qiao Li ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Amino Acid ◽  
Salvia Miltiorrhiza ◽  
Carthamus Tinctorius ◽  
Amino Acid Residues ◽  
Analysis Method ◽  
Effect Relationship ◽  
Relationship Analysis ◽  
Ms Analysis ◽  
Spectrum Effect

Tyrosinase (TYR) is a rate-limiting enzyme in the synthesis of melanin, while direct TYR inhibitors are a class of important clinical antimelanoma drugs. This study established a spectrum-effect relationship analysis method and high-performance liquid chromatography-mass spectrometry (LC-MS) analysis method to screen and identify the active ingredients that inhibited TYR in Salvia miltiorrhiza–Carthamus tinctorius (Danshen–Honghua, DH) herbal pair. Seventeen potential active compounds (peaks) in the extract of DH herbal pair were predicted, and thirteen of them were tentatively identified by LC-MS analysis. Furthermore, TYR inhibitory activities of five pure compounds obtained from the DH herbal pair were validated in the test in which kojic acid served as a positive control drug. Among them, three compounds including protocatechuic aldehyde, hydroxysafflor yellow A, and tanshinone IIA were verified to have high TYR inhibitory activity (IC50 value of 455, 498, and 1214 μM, resp.) and bind to the same amino acid residues in TYR catalytic pocket according to the results of the molecular docking test. However, the other two compounds lithospermic acid and salvianolic acid A had a weak effect on TYR, as they do not combine with the active amino acid residues or act on the active center of TYR. Therefore, the developed methods (spectrum-effect relationship analysis and molecular docking) could be used to effectively screen TYR inhibitors in complex mixtures such as natural products.

scholarly journals Synthesis and Molecular Docking Studies of Triazole Conjugated Novel 2,4-Disubstituted Thiazole Derivatives as CDK2 Inhibitors

2021 ◽  
Vol 33 (8) ◽  
pp. 1849-1854
Author(s):  
M. Narasimha ◽  
B. Revanth ◽  
D. Mahender ◽  
P. Sarita Rajender
Keyword(s):  
Molecular Docking ◽  
Amino Acid ◽  
Oral Absorption ◽  
Binding Capacity ◽  
Docking Studies ◽  
Thiazole Derivatives ◽  
Molecular Docking Studies ◽  
Mass Spectral ◽  
Drug Molecules ◽  
New Chemical Entities

A series of triazole conjugated novel 2,4-disubstituted thiazole derivatives (9a-l) were synthesized from salicylaldehyde. These new chemical entities were characterized by their IR, 1H & 13C NMR, mass spectral data and their molecular docking studies were performed to identify potential inhibitors of CDK2 protein. The synthesized analogs 9a-l were docked with CDK2 protein (PDB: 1GIJ). Among these 9h, 9j and 9k showed better Glide score, Prime MM-GBSA and ADME properties as compared to seliciclib and dinaciclib cancer inhibiting drugs of CDK2 protein. The amino acid Val83 of CDK2 protein was consistently binding to new chemical entities indicating that amino acid is crucial and responsible for its inhibition. Present findings suggested that compound 9h has 100% human oral absorption with highest Glide score -8.3kcal/mol whereas drug molecules have feebler binding capacity and less Glide score indicating that the synthesized new chemical entity as potential inhibitor for CDK2 protein.

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