http://www.biotech-asia.org/vol18no2/in-silico-modelling-of-1-3-3-substituted-phenyl-prop-2-enoyl-phenyl-thiourea-against-anti-inflammatory-drug-targets/

The main objective of this present study was to analyze the anti-inflammatory activity of the compound 1- 3- [3-(substituted phenyl) prop-2-enoyl) phenyl thiourea against inflammation receptors Secretory Phospholipase A2 (sPLA2-X), Cyclooxygenase-2 (COX-2), Interleukin-1 Receptor-associated Kinase 4 (IRAK4), Tumor Necrosis Factor (TNF-alpha) and Inducible Nitric Oxide Synthase 4 using various in-silico techniques. The 3D structures of the receptors were retrieved from Protein Data Bank in PDB format. The ligand molecule was sketched in Chemdraw Ultra v 10.0. The proteins and the ligand molecule were then individually prepared for docking using AutoDock Tools. Docking was performed using AutoDock Vina. Swiss-ADME and Pre-ADMET web servers were used for ADME, drug-likeness, and toxicity analysis. The receptor showing the best binding affinity with our ligand molecule was further analyzed via Molecular Dynamics (MD) Simulations using iMODS web server. The docking results revealed that our ligand molecule showed the best binding affinity with receptor sPLA2-X. The ADME analysis results of our ligand molecule were also good. MD Simulations study showed good results with our ligand- sPLA2-X receptor docked complex. This study revealed that our ligand molecule is a significant inhibitor sPLA2-X and can be further used as a potential therapy against inflammatory disorders.

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Drug Targets for Cardiovascular-Safe Anti-Inflammatory: In Silico Rational Drug Studies

PLoS ONE ◽

10.1371/journal.pone.0156156 ◽

2016 ◽

Vol 11 (6) ◽

pp. e0156156 ◽

Cited By ~ 4

Author(s):

Sajad Shahbazi ◽

Tammanna R. Sahrawat ◽

Monalisa Ray ◽

Swagatika Dash ◽

Dattatreya Kar ◽

...

Keyword(s):

In Silico ◽

Drug Targets ◽

Rational Drug ◽

Anti Inflammatory ◽

Drug Studies

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Natural Compound Modulates the Cervical Cancer Microenvironment—A Pharmacophore Guided Molecular Modelling Approaches

Journal of Clinical Medicine ◽

10.3390/jcm7120551 ◽

2018 ◽

Vol 7 (12) ◽

pp. 551 ◽

Cited By ~ 2

Author(s):

Shailima Rampogu ◽

Doneti Ravinder ◽

Smita Pawar ◽

Keun Lee

Keyword(s):

Cervical Cancer ◽

Md Simulations ◽

Data Bank ◽

Docking Studies ◽

New Drugs ◽

Binding Modes ◽

Cervical Cancer Cells ◽

Causative Agents ◽

Nitric Oxide Synthase 2 ◽

Oxide Synthase

Cervical cancer is regarded as one of the major burdens noticed in women next to breast cancer. Although, human papilloma viruses (HPVs) are regarded as the principal causative agents, they require certain other factors such as oestrogen hormone to induce cervical cancer. Aromatase is an enzyme that converts androgens into oestrogens and hindering this enzyme could subsequently hamper the formation of oestrogen thereby alleviating the disease. Accordingly, in the current investigation, a structure based pharmacophore was generated considering two proteins bearing the Protein Data Bank (PDB) codes 3EQM (pharm 1) and 3S7S (pharm 2), respectively. The two models were employed as the 3D query to screen the in-house built natural compounds database. The obtained 51 compounds were escalated to molecular docking studies to decipher on the binding affinities and to predict the quintessential binding modes which were affirmed by molecular dynamics (MD) simulations. The compound has induced dose-dependent down regulation of PP2B, Nitric oxide synthase-2 (NOS2), and Interleukin 6 (IL-6) genes in the HeLa cells and has modulated the expression of apoptotic genes such as Bax, Bcl2, and caspases-3 at different concentrations. These results guide us to comprehend that the identified aromatase inhibitor was effective against the cervical cancer cells and additionally could server as scaffolds in designing new drugs.

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Screening of Chloroquine, Hydroxychloroquine and Its Derivatives for Their Binding Affinity to Multiple SARS-CoV-2 Protein Drug Targets

10.26434/chemrxiv.12365282.v1 ◽

2020 ◽

Author(s):

Mallikarjuna Nimgampalle ◽

Vasudharani Devanthan ◽

Ambrish Saxena

Keyword(s):

Binding Affinity ◽

In Silico ◽

Drug Targets ◽

Therapeutic Potential ◽

Viral Proteins ◽

Protein Drug ◽

Potential Treatment ◽

Health Authorities ◽

Derivatives Of

Recently Chloroquine and its derivative Hydroxychloroquine have garnered enormous interest amongst the clinicians and health authorities’ world over as a potential treatment to contain COVID-19 pandemic. The present research aims at investigating the therapeutic potential of Chloroquine and its potent derivative Hydroxychloroquine against SARS-CoV-2 viral proteins. At the same time we have screened some chemically synthesized derivatives of Chloroquine and compared their binding efficacy with chemically synthesized Chloroquine derivatives through <i>in silico</i>approaches. For the purpose of the study, we have selected some essential viral proteins and enzymes implicated in SARS-CoV-2 replication and multiplication as putative drug targets.<br>

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IN SILICO ANTIMALARIAL TARGET SELECTION CONSERVED IN FOUR PLASMODIUM SPECIES

Universal Journal of Pharmaceutical Research ◽

10.22270/ujpr.v5i5.483 ◽

2020 ◽

Author(s):

Oladoja AWofisayo

Keyword(s):

Comparative Genomics ◽

Peer Review ◽

In Silico ◽

Drug Targets ◽

Homo Sapiens ◽

Mammalian Species ◽

Target Selection ◽

Plasmodium Species ◽

Data Bank ◽

Sequence Motifs

Objectives: The need for new antimalarials drugs and drug targets is pertinent due to the emergence of drug resistant strains of the parasites. Improper target selection has resulted in therapeutic failure. The genomic/post genomic era has made possible the deciphering of the 3D crystal structures of proteins and DNA which are drug targets and are deposited in the protein data bank. Methods: Novel antimalarial targets obtained from evolutionary conserved short sequence motifs are utilised and are essential in transcription processes in the parasite. The motifs TGCATGCA, GTGCAC and GTGCGTGC were curated from experimental work, validated and analysed via phylogenomics genomics and comparative genomics. PlasmoDB blastn was applied to determine their similarity in Plasmodium vivax, knowlesi, Ovale and yoeli. The complete genome of Plasmodium falciparum vivax, knowlesi, Ovale and yoeli was downloaded from the plasmoDB and their positions determined. Results: The targets are essential, conserved in rodent and mammalian species via phylogenomics with percentage identity and similarity greater than 80%, have no similar genes in the same genome and also found to be selective in the parasites vis-à-vis the Homo sapiens via comparative genomics with 0% identity and similarity in the human genome. Conclusion: The targets reveal at the molecular and biochemical level, the vulnerable regions in the parasite while safe in human hence their choices in subsequent rationale drug discovery and design protocols. Peer Review History: Received: 18 July 2020; Revised: 1 October; Accepted: 12 October, Available online: 15 November 2020 UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 7.0/10 Reviewer(s) detail: Dr. Tamer ELHABIBI, ERU University, Egypt, [email protected] Dr. Soroush Sardari, Biotech Pasteur Institute of Iran, Tehran, Iran, [email protected] Comments of reviewer(s): Similar Articles: IN SILICO LIGAND-BASED 2D PHARMACOPHORE GENERATION FOR H+/K+ ATPASE INHIBITORS

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Data for Molecular Dynamics Simulations of Escherichia Coli Cytochrome Bd Oxidase with the Amber Force Field

10.26434/chemrxiv.14488821.v1 ◽

2021 ◽

Author(s):

Surl-Hee Ahn ◽

Christian Seitz ◽

Vinicius Cruzeiro ◽

James McCammon ◽

Andreas Goetz

Keyword(s):

Escherichia Coli ◽

Molecular Dynamics ◽

Force Field ◽

Drug Targets ◽

Food Poisoning ◽

Md Simulations ◽

Data Bank ◽

Low Oxygen ◽

Amber Force Field ◽

E Coli

<div> <div> <div> <div> <p>Cytochrome <i>bd</i>-type quinol oxidase is an important metalloenzyme that allows many bacteria to survive in low oxygen conditions. Since bd oxidase is found in many prokaryotes but not in eukaryotes, it has emerged as a promising bacterial drug target. Examples of organisms containing bd oxidases include the <i>Mycobacterium tuberculosis (Mtb)</i> bacterium that causes tuberculosis (TB) in humans, the <i>Vibrio cholerae</i> bacterium that causes cholera, the <i>Pseudomonas aeruginosa</i> bacterium that contributes to antibiotic resistance and sepsis, and the <i>Campylobacter jejuni</i> bacterium that causes food poisoning. <i>Escherichia coli (E. coli)</i> is another organism exhibiting the cytochrome <i>bd</i> oxidase. Since it has the highest sequence identity to <i>Mtb</i> (36 %) and we are ultimately interested in finding drug targets for TB, we have built parameters for the <i>E. coli bd </i>oxidase (Protein Data Bank ID number: 6RKO) that are compatible with the all-atom Amber ff14SB force field for molecular dynamics (MD) simulations. Specifically, we built parameters for the three heme cofactors present in all species of bacterial cytochrome <i>bd</i>-type oxidases (heme b<sub>558</sub>, heme b<sub>595</sub>, and heme d) along with their axial ligands. This data report includes the parameter files that can be used with Amber's LEaP program to generate input files for MD simulations using the Amber software package. We also provide the PDB data files of the initial model both by itself and solvated with TIP3P water molecules and counterions. </p> </div> </div> </div> </div>

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Antinociceptive Activities and the Mechanisms of Anti-Inflammation of Asiatic Acid in Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2011/895857 ◽

2011 ◽

Vol 2011 ◽

pp. 1-10 ◽

Cited By ~ 53

Author(s):

Shyh-Shyun Huang ◽

Chuan-Sung Chiu ◽

Hsien-Jung Chen ◽

Wen-Chi Hou ◽

Ming-Jyh Sheu ◽

...

Keyword(s):

Nitric Oxide ◽

Interleukin 1 ◽

Late Phase ◽

Centella Asiatica ◽

Neutrophil Infiltration ◽

Asiatic Acid ◽

Pentacyclic Triterpene ◽

Cox 2 ◽

Anti Inflammatory ◽

Oxide Synthase

Asiatic acid (AA), a pentacyclic triterpene compound in the medicinal plantCentella asiatica, was evaluated for antinociceptive and anti-inflammatory effects. Treatment of male ICR mice with AA significantly inhibited the numbers of acetic acid-induced writhing responses and the formalin-induced pain in the late phase. In the anti-inflammatory test, AA decreased the paw edema at the 4th and 5th h afterλ-carrageenan (Carr) administration and increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the liver tissue. AA decreased the nitric oxide (NO), tumor necrosis factor-α(TNF-α), and interleukin-1β(IL-1β) levels on serum level at the 5th h after Carr injection. Western blotting revealed that AA decreased Carr-induced inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and nuclear factor-κB (NF-κB) expressions at the 5th h in the edema paw. An intraperitoneal (i.p.) injection treatment with AA also diminished neutrophil infiltration into sites of inflammation as did indomethacin (Indo). The anti-inflammatory mechanisms of AA might be related to the decrease in the level of MDA, iNOS, COX-2, and NF-κB in the edema paw via increasing the activities of CAT, SOD, and GPx in the liver.

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Estrogenic Effect of Scoparia dulcis (Linn) Extract in Mice Uterus and In Silico Molecular Docking Studies of Certain Compounds with Human Estrogen Receptors

Journal of Reproduction & Infertility ◽

10.18502/jri.v21i4.4329 ◽

2020 ◽

Author(s):

Khamhee Wangsa ◽

Indira Sarma ◽

Purbajyoti Saikia ◽

Dhanabalan Ananthakrishnan ◽

Hirendra Nath Sarma ◽

...

Keyword(s):

Molecular Docking ◽

Estrogen Receptors ◽

Binding Affinity ◽

In Silico ◽

Md Simulations ◽

Docking Studies ◽

Female Reproduction ◽

Molecular Docking Studies ◽

Scoparia Dulcis ◽

In Silico Molecular Docking

Background: Scoparia dulcis Linn. is reported to be used by women of Assam and Arunachal Pradesh in northeast India for treating menstrual disorders. Scoparia dulcis contains compounds that bind with estrogen receptors (ERα and ERβ) evidenced by increased PCNA in endometrial epithelium. Methods: Crude extract was orally administered at the dose of 500 mg/kg body weight/day to the female mice (60–70 days old) in five different groups. Each group containing six females included: (I) cyclic control, (II) cyclic extract treated, (III) Ovariectomized (OVX)-vehicle treated (Control), (IV) OVX-E2 treated (V) OVX- extract treated. Extract was administered for eight days to the cyclic groups and three days to the OVX groups. PCNA was detected immunohistochemically in uterine tiss ues and signals were analyzed by Image J software (NIH, USA). Compounds were separated by GC-MS and identified using NIST. In silico molecular docking studies was performed with human estrogen receptors (ERα and ERβ). Molecular dynamics (MD) simulations of the best interacting compound was done using gromacs. Results: The results showed cell proliferation in the uterine endometrium evidenced by PCNA. Two phytocompounds, Octadecanoic acid and methyl stearate showed binding affinity with ERα and ERβ. Conclusion: Scoparia dulcis contains compounds having binding affinity with ERα and ERβ. The present study is the first report on compounds from Scoparia dulcis showing binding affinity with human estrogen receptors which may have biological effect on female reproduction.

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Identification of Anti-Inflammatory and Anti-Proliferative Neolignanamides from Warburgia ugandensis Employing Multi-Target Affinity Ultrafiltration and LC-MS

Pharmaceuticals ◽

10.3390/ph14040313 ◽

2021 ◽

Vol 14 (4) ◽

pp. 313

Author(s):

Xiao-Cui Zhuang ◽

Yong-Li Zhang ◽

Gui-Lin Chen ◽

Ye Liu ◽

Xiao-Lan Hu ◽

...

Keyword(s):

Medicinal Plant ◽

Binding Affinity ◽

Proliferative Activity ◽

Topoisomerase I ◽

Drug Targets ◽

Spectroscopic Method ◽

Incidence And Mortality ◽

Medicinal Plant Extracts ◽

Cox 2 ◽

Anti Inflammatory

Previous reports have illustrated that the incidence and mortality of cancer are increasing year by year worldwide. In addition, the occurrence, development, recurrence and metastasis of cancer are closely related to inflammation, which is a kind of defensive response of human body to various stimuli. As an important medicinal plant in Africa, Warburgia ugandensis has been reported to have certain anti-inflammatory and anti-proliferative activities, but its specific components and mechanisms of action remain elusive. To tackle this challenge, affinity ultrafiltration with drug targets of interest coupled to high-performance liquid chromatography-mass spectrometry (AUF-HPLC-MS/MS) could be utilized to quickly screen out bioactive constituents as ligands against target enzymes from complex extracts of this plant. AUF-HPLC-MS/MS with four drug targets, i.e., cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), topoisomerase I (Top I) and topoisomerase II (Top II) were used to rapidly screen and characterize the anti-inflammatory and anti-proliferative natural ligands from W. ugandensis, and the resulting potential active compounds as ligands with specific binding affinity to COX-2, 5-LOX, Top I and Top II, were isolated with modern separation and purification techniques and identified with spectroscopic method like NMR, and then their antiinflammatory and anti-proliferative activities were tested to verify the screening results from AUF-HPLC-MS/MS. Compounds 1 and 2, which screened out and identified from W. ugandensis showed remarkable binding affinity to COX-2, 5-LOX, Top I and Top II with AUF-HPLC-MS/MS. In addition, 1 new compound (compound 3), together with 5 known compounds were also isolated and identified from W. ugandensis. The structure of compound 3 was elucidated by extensive 1D, 2D NMR data and UPLC-QTOF-MS/MS. Furthermore, compounds 1 and 2 were further proved to possess both anti-inflammatory and anti-proliferative activities which are in good agreement with the screening results using AUF-HPLC-MS/MS. This work showcased an efficient method for quickly screening out bioactive components with anti-inflammatory and anti-proliferative activity from complex medicinal plant extracts using AUF-HPLC-MS/MS with target enzymes of interest, and also demonstrated that neolignanamides (compounds 1 and 2) from W. ugandensis would be the active components responsible for its anti-inflammatory and anti-proliferative activity with the potential to treat cancer and inflammation.

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ANTI-INFLAMMATORY ACTIVITY OF SYZYGIUM AROMATICUM SILVER NANOPARTICLES: IN VITRO AND IN SILICO STUDY

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i11.19904 ◽

2017 ◽

Vol 10 (11) ◽

pp. 370 ◽

Cited By ~ 2

Author(s):

Reslee Elsa Varghese ◽

Ragavan D ◽

Saranya Sivaraj ◽

Dasararaju Gayathri ◽

Gomathi Kannayiram

Keyword(s):

Silver Nanoparticles ◽

Aqueous Extract ◽

In Silico ◽

Protein Denaturation ◽

Interleukin 1 ◽

Antioxidant Property ◽

Inflammatory Activity ◽

Enzyme Linked Immunosorbent Assay ◽

Syzygium Aromaticum ◽

Anti Inflammatory

Objective: In the present study, antioxidant and anti-inflammatory activity of Syzygium aromaticum (clove) silver nanoparticles (clove AgNP’s) was evaluated.Methods: Gas chromatography-mass spectrometry technique was used to identify the compounds present in the aqueous extract of clove. Fourier transform infrared (FT-IR) analysis was done to characterize the clove silver AgNP’s. 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay was performed to evaluate the antioxidant property of nanoparticles (0.05 and 0.25 mg/ml) and aqueous extracts (0.05, 0.1, and 0.25 mg/ml) of clove. The anti-inflammatory property of the clove AgNP’s was determined by inhibition of protein denaturation and downregulation of interleukin-1 beta. In silico molecular docking studies was performed using Schrodinger Maestro software.Results: Eugenol was found to be highest with 16.27%. The AgNP’s exhibited dose-dependent antioxidant property. AgNP’s scavenged 80% of radical at the concentration of 0.25 mg/ml. The scavenging activity of AgNP’s markedly increased when compared to aqueous extract at the same concentration. Inhibition of protein denaturation assay also revealed AgNP’s showing the highest activity (66%) when compared with drug aspirin (55%) and aqueous extract (56%). In the enzyme-linked immunosorbent assay (ELISA) method, AgNP’s showed better inhibition (80%) when compared to aqueous extract (60%). Among 15 compounds, two compounds (eugenol and methyl 14-methylpentadecanoate) showed good glide energy, docking score, and hydrogen-bonded active site interactions with the protein interleukin-1 beta.Conclusion: As AgNP’s were more active than the aqueous extract, it may be considered for pharmacological activity against inflammatory disorders.

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