Antimalarial Flavonoid-Glycoside from Acacia pennata with Inhibitory Potential Against PfDHFR-TS: An In-silico Study

Drug resistance, toxicity, and adverse effects of current antimalarial drugs have mandated the need to search for newer antimalarial agents. The present study aims to identify promising flavonoid-glycosides (FGs) from Acacia pennata as possible antimalarial agents effective against PfDHFR-TS (PDB ID: 3DGA) by in-silico studies. The co-crystal inhibitor (RJ1) of PfDHFR-TS was used as the reference standard compound. A compound library of 17 FGs reported to be isolated from A. pennata was prepared and subjected to molecular docking simulation studies. PyRx 0.8 and AutoDock Vina revealed Pinocembrin-7-O-β-D-glucopyranoside (FG17) as the best PfDHFR-TS inhibitor with a binding affinity of -10.4 kcal/mol and -10.8 kcal/mol, respectively. In both methods, FG17 has a better binding affinity than the co-crystal inhibitor, RJ1 (-7.9 kcal/mol). The docking protocols were validated by RMSD calculation with Discovery Studio Visualizer software (2020). FG17 interacted with amino acids ALA16, LEU40, SER167, GLY41, GLY44, MET55, PHE58, ILE112, LEU119, GLY166, and TYR170 at the active binding site of PfDHFR-TS. Further, FG17 was computed as a non-toxic, bioavailable, synthetically accessible compound and a better enzyme inhibitor than RJ1. Hence, we conclude that FG17 may be used as a lead scaffold to design antimalarial agents against PfDHFR-TS in the future.

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APPLICATION OF IN SILICO STUDIES TARGETING TELOMERIC G-QUADRUPLEX COMPLEX BY PERYLENE DIIMIDES FOR ANTICANCER THERAPY

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11s4.31680 ◽

2018 ◽

Vol 11 ◽

Author(s):

Hemalatha Cn, ◽

Vijey Aanandhi M

Keyword(s):

Binding Affinity ◽

In Silico ◽

Data Bank ◽

Anticancer Therapy ◽

Standard Drug ◽

Perylene Diimides ◽

Discovery Studio ◽

In Silico Studies ◽

G Quadruplex ◽

Ic50 Values

Objective: Telomerase enzyme which is expressed in detectable levels and its mechanism was that it increases the length when it binds to telomeres. This eventually leads to extension of lifespan of cells and also makes an attractive target for cancer therapy. Perylene diimides bind to telomerase with duplex genomic DNA, and these G-quadruplex ligands are of responsible for binding affinity with respective proteins. Based on the IC50 values of perylene diimides, QSAR has been studied out and the results are elaborated in preliminary research works. From the results of QSAR, the selected perylene ligands are selected for docking choosing telomerase as a target/protein. From the results of in silico studies, new compounds are designed and synthesized accordingly. Now, the objective of the study was to dock the final synthesized compounds with the telomerase protein to study regarding the pKi value using G-quadruplex ligand database (G4LDB). The docked results are visualized using Discovery Studio Visualizer 4.1. The results are compared with the standard N,N’-bis-(2-(1-piperidino)ethyl)-3,4,9,10-perylene tetracarboxylic acid diimide (PIPER) drug and these compounds will be effective for anticancer therapy.Methods: The study was to investigate the docking results of synthesized perylene compounds with the results from G4LDB and visualized by Discovery Studio 4.1 Visualizer. The telomerase proteins selected for the study were extracted from Protein Data Bank, and the proteins selected for the study are 3SC8 and 3CE5. Among the compounds (R1, R2, R3, and R4) screened in G-Quadruplex Ligand Database, compound R3 shows better binding affinity with good pKi value as well the interactions with the protein and ligand show better affinity with the targets and these are compared with the standard drug PIPER drug.Results: Compound R3 possesses the best binding affinity with the target 3CE5 and 3SC8 which shows that the compound will be effective for anticancer therapy.

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Anti-MRSA Constituents from Ruta chalepensis (Rutaceae) Grown in Iraq, and In Silico Studies on Two of Most Active Compounds, Chalepensin and 6-Hydroxy-rutin 3′,7-Dimethyl ether

Molecules ◽

10.3390/molecules26041114 ◽

2021 ◽

Vol 26 (4) ◽

pp. 1114 ◽

Cited By ~ 1

Author(s):

Shaymaa Al-Majmaie ◽

Lutfun Nahar ◽

M. Mukhlesur Rahman ◽

Sushmita Nath ◽

Priyanka Saha ◽

...

Keyword(s):

Dimethyl Ether ◽

In Silico ◽

Efflux Pump ◽

Perennial Herb ◽

Flavonoid Glycosides ◽

Cinnamic Acid Derivative ◽

Active Compounds ◽

Ruta Chalepensis ◽

In Silico Studies ◽

Mrsa Strains

Ruta chalepensis L. (Rutaceae), a perennial herb with wild and cultivated habitats, is well known for its traditional uses as an anti-inflammatory, analgesic, antipyretic agent, and in the treatment of rheumatism, nerve diseases, neuralgia, dropsy, convulsions and mental disorders. The antimicrobial activities of the crude extracts from the fruits, leaves, stem and roots of R. chalepensis were initially evaluated against two Gram-positive and two Gram-negative bacterial strains and a strain of the fungus Candida albicans. Phytochemical investigation afforded 19 compounds, including alkaloids, coumarins, flavonoid glycosides, a cinnamic acid derivative and a long-chain alkane. These compounds were tested against a panel of methicillin-resistant Staphylococcus aureus (MRSA) strains, i.e., ATCC 25923, SA-1199B, XU212, MRSA-274819 and EMRSA-15. The MIC values of the active compounds, chalepin (9), chalepensin (10), rutamarin (11), rutin 3′-methyl ether (14), rutin 7,4′-dimethyl ether (15), 6-hydroxy-rutin 3′,7-dimethyl ether (16) and arborinine (18) were in the range of 32–128 µg/mL against the tested MRSA strains. Compounds 10 and 16 were the most active compounds from R. chalepensis, and were active against four out of six tested MRSA strains, and in silico studies were performed on these compounds. The anti-MRSA activity of compound 16 was comparable to that of the positive control norfloxacin (MICs 32 vs 16 μg/mL, respectively) against the MRSA strain XU212, which is a Kuwaiti hospital isolate that possesses the TetK tetracycline efflux pump. This is the first report on the anti-MRSA property of compounds isolated from R. chalepensis and relevant in silico studies on the most active compounds.

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In-silico Molecular Docking and ADME/Pharmacokinetic Prediction Studies of Some Novel Carboxamide Derivatives as Anti-tubercular Agents

Chemistry Africa ◽

10.1007/s42250-020-00162-3 ◽

2020 ◽

Vol 3 (4) ◽

pp. 989-1000

Author(s):

Mustapha Abdullahi ◽

Shola Elijah Adeniji

Keyword(s):

Molecular Docking ◽

Binding Affinity ◽

In Silico ◽

Density Functional ◽

Docking Simulation ◽

Basis Set ◽

Hybrid Functional ◽

Standard Drug

AbstractMolecular docking simulation of thirty-five (35) molecules of N-(2-phenoxy)ethyl imidazo[1,2-a]pyridine-3-carboxamide (IPA) with Mycobacterium tuberculosis target (DNA gyrase) was carried out so as to evaluate their theoretical binding affinities. The chemical structure of the molecules was accurately drawn using ChemDraw Ultra software, then optimized at density functional theory (DFT) using Becke’s three-parameter Lee–Yang–Parr hybrid functional (B3LYP/6-311**) basis set in a vacuum of Spartan 14 software. Subsequently, the docking operation was carried out using PyRx virtual screening software. Molecule 35 (M35) with the highest binding affinity of − 7.2 kcal/mol was selected as the lead molecule for structural modification which led to the development of four (4) newly hypothetical molecules D1, D2, D3 and D4. In addition, the D4 molecule with the highest binding affinity value of − 9.4 kcal/mol formed more H-bond interactions signifying better orientation of the ligand in the binding site compared to M35 and isoniazid standard drug. In-silico ADME and drug-likeness prediction of the molecules showed good pharmacokinetic properties having high gastrointestinal absorption, orally bioavailable, and less toxic. The outcome of the present research strengthens the relevance of these compounds as promising lead candidates for the treatment of multidrug-resistant tuberculosis which could help the medicinal chemists and pharmaceutical professionals in further designing and synthesis of more potent drug candidates. Moreover, the research also encouraged the in vivo and in vitro evaluation study for the proposed designed compounds to validate the computational findings.

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In-Silico Study of Some Natural Plant Phyto-compounds for the Identification of Novel Potent Cholinesterase Inhibitors Against Alzheimer Disease

10.20944/preprints202108.0403.v1 ◽

2021 ◽

Author(s):

Dhiraj Kumar ◽

Sanjana Bhagat

Keyword(s):

Binding Affinity ◽

In Silico ◽

Docking Study ◽

Inhibitory Effect ◽

Ache Inhibitor ◽

Site Analysis ◽

Strong Binding ◽

In Silico Studies ◽

Potent Inhibitory Effect ◽

Autodock 4.0

The main aim of this study is to identify inhibitory binding potent of the available commercially alkaloids, against the crystal structure of acetylcholinesterase (AChE) protein by in silico studies. The inhibitory data of the compounds should be compared with the internal ligand as well as standard AChE inhibitor Aricept (which is used for the treatment of all stages of Alzheimer’s disease). AutoDock 4.0 is used for the docking study, conformational orientation site analysis, and, with the help of docking, we have calculated parameters like binding energy and inhibition constant. Docking's study showed that Glabridin, Isorosmanol, Quercetin, Honokiol, Eckol, Sargaquinoic acid, and Ginsedosides revealed strong binding affinity with the enzyme. Moreover, The ADMET profiling and physicochemical properties of the selected compounds are evaluated using the Molinspiration and Data warrior software. By showing a strong binding affinity value, positive bioactivity score, and good pharmacokinetic properties, the top compound was determined. After evaluation with all parameters, the compound Glabridin and Ginsedosides show the most potent inhibitory effect towards the acetylcholinesterase, so this compound could be used as a novel is required to treat Alzheimer's disease.

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SYNTHESIS, INSILICO DOCKING AND ADMET STUDIES OF ARYL ACETIC ACID DERIVATIVES AS PROSTAGLANDIN ENDOPEROXIDE H SYNTHASE-2 INHIBITORS

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i4.15287 ◽

2017 ◽

Vol 10 (4) ◽

pp. 68

Author(s):

Abirami Kandhaswamy ◽

Saravanan Rangan ◽

Irshad Ahmed ◽

Ks Meena Mohan

Keyword(s):

Liquid Chromatography ◽

In Silico ◽

Glycidyl Ether ◽

High Yield ◽

Discovery Studio ◽

In Silico Docking ◽

Prostaglandin Endoperoxide ◽

In Silico Studies ◽

Anti Inflammatory ◽

Endoperoxide H Synthase

Objectives: To study the inhibition of prostaglandin endoperoxide H synthase-2 (PHSH-2) for arylacetic acid derivatives. Methods: This study was performed to evaluate the anti-inflammatory activity of the synthesized arylacetic acid erivatives through molecular docking via Discovery Studio 4.0 and Schrodinger Software. ADMET study was conducted to find the assessment on genotoxicology.Results: The synthesized arylacetic acid derivatives were confirmed by nuclear magnetic resonance, liquid chromatography-mass spectrometry, and purity by high-performance liquid chromatography. The synthetic pathway is economical, industrial scalability and is achieved with high yield and purity. The in silico studies identified the active pocket and compared with the standard drug.Conclusion: Results from this work conclude that the arylacetic acid derivatives have very good inhibition and very low binding energy toward the active pocket, hence can be considered as good inhibitors of PHSH-2 on comparison with iodosuprofen. The compounds qualified Lipinski rule of five and the ADMET results were non-mutagenic and non-carcinogenic.Keywords: Arylacetic acid, 1 phenyl glycidyl ether protein, ADMET, In silico docking, Anti-inflammatory.

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Copper-Catalyzed Synthesis, Bio-Evaluation, and in Silico Studies of 2-Aryl-N-alkylbenzimidazoles as Neuroprotective Agents

Catalysts ◽

10.3390/catal8100433 ◽

2018 ◽

Vol 8 (10) ◽

pp. 433 ◽

Cited By ~ 2

Author(s):

Yun-Xin Yao ◽

Nan-Nan Jia ◽

Ya-Nan Cao ◽

Xing-Xiu Chen ◽

Feng Gao ◽

...

Keyword(s):

In Silico ◽

Topoisomerase Ii ◽

Metabotropic Glutamate Receptor ◽

Docking Simulation ◽

Histone Deacetylase 6 ◽

Metabotropic Glutamate ◽

Aryl Bromides ◽

Protein Receptor ◽

In Silico Studies

2-aryl-N-alkylbenzimidazole derivatives synthesized by CuI/PPh3 promoted direct coupling of N-alkylbenzimidazoles with aryl bromides. In vitro neurotoxicities of 20 compounds were evaluated, and the neuroprotective abilities of low-neurotoxic compounds (3b, 3g, 3h, 3i, 3j, 3k, 3o, 3q, 3s and 3t) were investigated against toxicity induced by 1-methyl-4-phenylpyridinium ion (MPP+) in SH-SY5Y neuronal cells. In silico studies revealed that compound 3g could have molecule docking with the following proteins: the bone morphogenetic protein receptor type 1B (BMPR1B), human cytochrome P450 1B1(CYP1B1), Metabotropic glutamate receptor 7 (GRM7), histone deacetylase 6 (HDAC6), 5-hydroxytryptamine receptor 5A (HTR5A), human topoisomerase II beta (TOP2B). A molecular docking simulation of model compound 3g and model protein CYP1B1 has been shown.

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Computational Study of the Therapeutic Potential of Novel Heterocyclic Derivatives against SARS-CoV-2

COVID ◽

10.3390/covid1040061 ◽

2021 ◽

Vol 1 (4) ◽

pp. 757-774

Author(s):

Benjamin Ayodipupo Babalola ◽

Tosin Emmanuel Adetobi ◽

Oluwamayowa Samuel Akinsuyi ◽

Otunba Ahmed Adebisi ◽

Elizabeth Oreoluwa Folajimi

Keyword(s):

Binding Affinity ◽

Drug Targets ◽

Therapeutic Potential ◽

Computational Study ◽

Docking Simulation ◽

Therapeutic Interventions ◽

Binding Motif ◽

Therapeutic Benefits ◽

Heterocyclic Derivatives ◽

Inhibitory Potential

Severe Acute Respiratory Syndrome Coronavirus- 2 (SARS-CoV-2), including the recently reported severe variant B.1.617.2, has been reported to attack the respiratory tract with symptoms that may ultimately lead to death. While studies have been conducted to evaluate therapeutic interventions against the virus, this study evaluated the inhibitory potential of virtually screened novel derivatives and structurally similar compounds towards SARS-CoV-2 via a computational approach. A molecular docking simulation of the inhibitory potentials of the compounds against the SARS-CoV-2 drug targets—main protease (Mpro), spike protein (Spro), and RNA-dependent RNA polymerase (RdRp)—were evaluated and achieved utilizing AutoDock Vina in PyRx workspace. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of these compounds were assessed using SwissADME and ADMETLab servers. All the compounds displayed high binding affinities for the SARS-CoV-2 drug targets. However, the C13 exhibited the highest binding affinity for the drug targets, Spro and RdRp, while C15 exhibited the highest binding affinity for Mpro. The compounds interacted with the LEU A:271, LEU A:287, ASP A:289, and LEU A:272 of Mpro and the HIS A:540, PRO A:415, PHE A:486, and LEU A:370 of the Spro receptor binding motif and some active site amino acids of RdRp. The compounds also possess a favourable ADMET profile and showed no tendency towards hERG inhibition, hepatotoxicity, carcinogenicity, mutagenicity, or drug-liver injury. These novel compounds could offer therapeutic benefits against SARS-CoV-2, and wet laboratory experiments are necessary to further validate the results of this computational study.

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Combination of Curcumin from Curcuma longa and Procyanidin from Tamarindus indica in Inhibiting Cyclooxygenases for Primary Dysmenorrhea Therapy: In silico study

Biointerface Research in Applied Chemistry ◽

10.33263/briac111.74607467 ◽

2020 ◽

Vol 11 (1) ◽

pp. 7460-7467

Keyword(s):

Binding Affinity ◽

Bioactive Compounds ◽

In Silico ◽

Curcuma Longa ◽

Complex Form ◽

Bioactive Compound ◽

Primary Dysmenorrhea ◽

Tamarindus Indica ◽

Ligand Interaction ◽

Discovery Studio

Turmeric (Curcuma longa) and Tamarind (Tamarindus indica) are known for the anti-inflammatory and antioxidant activity. The major bioactive compound found in turmeric is curcumin, and tamarind is procyanidin. Both compounds could reduce prostaglandin concentration, leading to the reduction of primary dysmenorrhea by inhibiting COXs. This study aims to identify the interaction of tamarind and turmeric bioactive compounds as single isolated compound and complex compounds to COXs using in silico as a model study. Proteins and bioactive compounds were obtained from PDB database and Pubchem, respectively. Both proteins and ligands will be prepared using Discovery Studio Client 3.5 and PyRx 0.8. The interaction will be performed by docking using Autodock Vina in PyRx 0.8. It showed that turmeric and tamarind bioactive compounds in single isolated form have potency in inhibiting COX-1/COX-2, and both ligands bind to the catalytic site of proteins. Binding sites are surrounding the binding site of the natural substrate with an efficient binding affinity. In the complex form of turmeric-tamarind, the binding affinity is not as efficient as single compounds. However, its complex form of both compounds provides strong inhibition. This study suggested that complex forms of curcumin and procyanidin can reduce prostaglandin concentration and stabilize protein-ligand interaction lead to healing dysmenorrhea.

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Evaluation and Elucidation of Bioactive Compounds from Leptogium rivurale Through in-vitro and in-silico Studies

Proceedings International ◽

10.33263/proceedings21.010010 ◽

2020 ◽

Vol 2 (1) ◽

pp. 10

Keyword(s):

Aqueous Extract ◽

In Silico ◽

Methanol Extract ◽

Radical Scavenging Activity ◽

Radical Scavenging ◽

Docking Simulation ◽

Bioactive Constituents ◽

Drug Candidates ◽

In Silico Studies

Leptoguium rivurale is a flooded jelly skin lichen, the surface of which becomes jelly when wet. It is a cyanolichen in which the photosynthetic partner is a cyanobacterium in the genus name Nostac. The present study was performed to investigate the bioactive constituents of Leptoguium rivurale. Samples were collected from forest regions of Kodaikanal. The collected Lichens were washed and dried and then extracted by using methanol and distilled water. Qualitative analysis of phytochemicals from the extracts showed the presence of carbohydrates, glycosides, phenols, terpenoids, saponins, and proteins. The amount of carbohydrates, phenols, and proteins was found to 350u/g and 380u/g, 200u/g, and 240u/g and 490u/g and 320u/g in aqueous and methanol extracts. The α-amylase enzyme inhibition assay ranged from 47.2% to 58.4% for methanol extract and from 35.12% to 51.1% for aqueous extract. The DPPH radical scavenging activity ranged from 27.6% to 49.8% for methanol extract and from 21.3% to 42.2% for aqueous extract. The anti-inflammatory activity ranged from 40.5% to 86.2% for methanol extract and from 49.4% to 79.2% for aqueous extract. Then the extract was given for GC-MS analysis. The molecules that were obtained in this analysis were used as ligands and in-silico molecular docking simulation was made using AutoDock software through which it was found that out of the docked ligands cyclohexanol and oxirane were the potential drug candidates.

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