scholarly journals In Silico Biology of H1N1: Molecular Modelling of Novel Receptors and Docking Studies of Inhibitors to Reveal New Insight in Flu Treatment

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Deepak Kumar Behera ◽  
Pabitra Mohan Behera ◽  
Laxmikanta Acharya ◽  
Anshuman Dixit ◽  
Payodhar Padhi
Keyword(s):  
Sialic Acid ◽  
Lipid Membrane ◽  
Oral Absorption ◽  
Docking Studies ◽  
Eastern India ◽  
The Family ◽  
In Silico Biology ◽  
Host Cell Surface ◽  
Genetic Combination ◽  
Homology Models

Influenza is an infectious disease caused by RNA viruses of the family Orthomyxoviridae. The new influenza H1N1 viral stain has emerged by the genetic combination of genes from human, pig, and bird’s H1N1 virus. The influenza virus is roughly spherical and is enveloped by a lipid membrane. There are two glycoproteins in this lipid membrane; namely, hemagglutinin (HA) which helps in attachment of the viral strain on the host cell surface and neuraminidase (NA) that is responsible for initiation of viral infection. We have developed homology models of both Hemagglutinin and Neuraminidase receptors from H1N1 strains in eastern India. The docking studies of B-Sialic acid and O-Sialic acid in the optimized and energy-minimized homology models show important H-bonding interactions with ALA142, ASP230, GLN231, GLU232, and THR141. This information can be used for structure-based and pharmacophore-based new drug design. We have also calculated ADME properties (Human Oral Absorption (HOA) and % HOA) for Oseltamivir which have been subject of debate for long.

scholarly journals Synthesis, Bioactivity, Pharmacokinetic and Biomimetic Properties of Multi-Substituted Coumarin Derivatives

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5999
Author(s):  
Annita Katopodi ◽  
Evangelia Tsotsou ◽  
Triantafylia Iliou ◽  
Georgia-Eirini Deligiannidou ◽  
Eleni Pontiki ◽  
...  
Keyword(s):  
Cell Viability ◽  
Oral Absorption ◽  
Radical Scavenging ◽  
Human Keratinocytes ◽  
Docking Studies ◽  
Hydroxyl Group ◽  
Coumarin Derivatives ◽  
In Silico Docking ◽  
A375 Cells

A series of novel multi-substituted coumarin derivatives were synthesized, spectroscopically characterized, and evaluated for their antioxidant activity, soybean lipoxygenase (LOX) inhibitory ability, their influence on cell viability in immortalized human keratinocytes (HaCaT), and cytotoxicity in adenocarcinomic human alveolar basal epithelial cells (A549) and human melanoma (A375) cells, in vitro. Coumarin analogues 4a–4f, bearing a hydroxyl group at position 5 of the coumarin scaffold and halogen substituents at the 3-phenyl ring, were the most promising ABTS•+ scavengers. 6,8-Dibromo-3-(4-hydroxyphenyl)-4-methyl-chromen-2-one (4k) and 6-bromo-3-(4,5-diacetyloxyphenyl)-4-methyl-chromen-2-one (3m) exhibited significant lipid peroxidation inhibitory activity (IC50 36.9 and 37.1 μM). In the DCF-DA assay, the 4′-fluoro-substituted compound 3f (100%), and the 6-bromo substituted compounds 3i (80.9%) and 4i (100%) presented the highest activity. The 3′-fluoro-substituted coumarins 3e and 4e, along with 3-(4-acetyloxyphenyl)-6,8-dibromo-4-methyl-chromen-2-one (3k), were the most potent lipoxygenase (LOX) inhibitors (IC50 11.4, 4.1, and 8.7 μM, respectively) while displaying remarkable hydroxyl radical scavenging ability, 85.2%, 100%, and 92.9%, respectively. in silico docking studies of compounds 4e and 3k, revealed that they present allosteric interactions with the enzyme. The majority of the analogues (100 μΜ) did not affect the cell viability of HaCaT cells, though several compounds presented over 60% cytotoxicity in A549 or A375 cells. Finally, the human oral absorption (%HOA) and plasma protein binding (%PPB) properties of the synthesized coumarins were also estimated using biomimetic chromatography, and all compounds presented high %HOA (>99%) and %PPB (60–97%) values.

Recombinant sialidase NanA (rNanA) cleaves α2-3 linked sialic acid of host cell surface N-linked glycoprotein to promote Edwardsiella tarda infection

2015 ◽  
Vol 47 (1) ◽  
pp. 34-45 ◽  
Author(s):  
Petros Kingstone Chigwechokha ◽  
Mutsumi Tabata ◽  
Sayaka Shinyoshi ◽  
Kazuki Oishi ◽  
Kyosuke Araki ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Cell Surface ◽  
Host Cell ◽  
Edwardsiella Tarda ◽  
Host Cell Surface

scholarly journals Alternative attachment factors and internalization pathways for GIII.2 bovine noroviruses

2011 ◽  
Vol 92 (6) ◽  
pp. 1398-1409 ◽  
Author(s):  
Axel Mauroy ◽  
Laurent Gillet ◽  
Elisabeth Mathijs ◽  
Alain Vanderplasschen ◽  
Etienne Thiry
Keyword(s):  
Sialic Acid ◽  
Sodium Periodate ◽  
Kidney Cells ◽  
Bovine Kidney ◽  
Host Interactions ◽  
Bovine Cell ◽  
Genotype 2 ◽  
The Family ◽  
Dependent Pathway

Bovine noroviruses belong to the family Caliciviridae, genus Norovirus. Two genotypes have been described and viruses genetically related to the Jena and Newbury2 strains have been classified into genotypes 1 and 2, respectively. In this study, virus-like particles (VLP) of the previously detected B309 Belgian strain, genetically related to genotype 2 bovine noroviruses, were used to investigate virus–host interactions in vitro. B309 VLP were shown to bind to several bovine cell lines. This binding was not affected by heparinase or chondroitinase treatment but was significantly inhibited by both sodium periodate, α-galactosidase, trypsin and phospholipase C treatment. Cell treatment by neuraminidase also moderately affected this binding. Taken together, these results show that, in addition to a galactosyl residue, sialic acid could also be involved in binding to susceptible cells. In addition, both the cholesterol-dependent pathway and macropinocytosis are used for B309 VLP internalization by Madin–Darby bovine kidney cells. The data increase the knowledge on bovine norovirus cell interactions.

scholarly journals High Throughput Prediction of Oral Absorption: Improvement of the Composition of the Lipid Solution Used in Parallel Artificial Membrane Permeation Assay

2001 ◽  
Vol 6 (3) ◽  
pp. 189-196 ◽  
Author(s):  
Kiyohiko Sugano ◽  
Hirokazu Hamada ◽  
Minoru Machida ◽  
Hidetoshi Ushio
Keyword(s):  
Stearic Acid ◽  
Chain Length ◽  
Lipid Membrane ◽  
Negative Charge ◽  
Oral Absorption ◽  
Membrane Permeation ◽  
Artificial Membrane ◽  
Intestinal Membrane ◽  
Charged Membrane ◽  
Precise Prediction

The purpose of the present study was to improve the composition of the lipid solution used in parallel artificial membrane permeation assay for the precise prediction of oral absorption. We modified the composition of lipid solution, which was used to make a lipid membrane on the filter support. First, we changed the chain length of organic solvent (PC/alkyldienes [C7-C10]). A negative charge was then added to the membrane to mimic the intestinal membrane (PC/stearic acid/1,7-octadiene and PC/PE/PS/PI/cholesterol/1,7-octadiene). Finally, we examined the predictability of the PC/PE/PS/PI/CHO/1,7-octadiene membrane using structurally diverse compounds. Permeability coefficients of tested compounds were increased as the chain length of alkyldiene became shorter. The addition of a negative charge to the membrane increased the permeability of the basic compounds. However, the negatively charged membrane with stearic acid showed different permeability profiles from PC/PE/PSIPI/CHO. The predictability of the PC/PE/PS/PI/CHO/1,7-octadiene membrane was adequate (r = 0.858, n = 31) for use during the early stages of the drug discovery/development process.

scholarly journals α2,6-Linked sialic acid acts as a receptor for Feline calicivirus

2007 ◽  
Vol 88 (1) ◽  
pp. 177-186 ◽  
Author(s):  
Amanda D. Stuart ◽  
T. David K. Brown
Keyword(s):  
Sialic Acid ◽  
Adhesion Molecule ◽  
Sodium Periodate ◽  
Metabolic Inhibitors ◽  
Feline Calicivirus ◽  
Sambucus Nigra ◽  
Virus Binding ◽  
Maackia Amurensis ◽  
The Family

Feline calicivirus (FCV) is a major causative agent of respiratory disease in cats. It is also one of the few cultivatable members of the family Caliciviridae. It has recently been reported that FCV binding is in part due to interaction with junction adhesion molecule-A. This report describes the characterization of additional receptor components for FCV. Chemical treatment of cells with sodium periodate showed that FCV recognized carbohydrate moieties on the surface of permissive cells. Enzymic treatment with Vibrio cholerae neuraminidase demonstrated that sialic acid was a major determinant of virus binding. Further characterization using linkage-specific lectins from Maackia amurensis and Sambucus nigra revealed that FCV recognized sialic acid with an α2,6 linkage. Using various proteases and metabolic inhibitors, it was shown that α2,6-linked sialic acid recognized by FCV is present on an N-linked glycoprotein.

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.

scholarly journals Synthesis, Spectral Characterization, in Vitro and in Silico Studies of Benzodioxin Pyrazoline derivatives

2020 ◽  
Vol 11 (2) ◽  
pp. 9126-9138
Keyword(s):  
Breast Cancer ◽  
In Silico ◽  
Oral Absorption ◽  
Docking Studies ◽  
In Vitro Studies ◽  
Bacterial Protein ◽  
Online Tools ◽  
In Silico Studies ◽  
Theoretical Results

The present study deals with the in silico and in vitro studies of DBDP derivatives, which is formed from the Michal-addition reaction of DihydroBenzo[b]Dioxin Chalcone Derivatives(DBDD) with hydrazine hydrate and carboxyethane. The DBDD were synthesized via Claisen condensation between substituted aldehyde and 1,4-(benzodioxan-6-yl)-methyl ketone. The newly arrived compounds were characterized by IR and NMR spectra. The structurally confirmed synthesized compounds were screened against 1UAG microbial protein, 1OQA cancer protein using auto dock software, and ADME properties also found by using (in silico) Swissadme and Molinspiration online tools. All the newly arrived DBDP compounds have passed the acceptable values of ADME (drug-likeness), medicinal property, and lead likeness in ADME prediction. Compound DBDP-9 scored better values in drug-likeness. It obeys the five basic rules (Lipinski, Ghose, Verber, Egan, and Muegge) of medicinal chemistry property, passed the PAINS, Brenk filters with 0 violation, and also have better lead likeness value. All the other compounds in this series also passed the above-mentioned properties with 1 or 2 violations only present in PAINS and Brenk filter. This theoretical results incitement to performed docking and in vitro studies of the DBDP derivatives. Docking studies results that the good I.S averse to 1 UAG bacterial protein than standard drugs and also give impact values in the docking against 1OQA breast cancer protein. Overall observation from the above studies, DBDP-9 has a maximum oral absorption value 91.36% with 0 violation alert in drug-likeness, medicinal property, and pharmacokinetics filter. DBDP-4 has a good I.S (-8.8), DBDP-2 has 4 numbers of HBI as standard, and all the DBDP 1-9 compounds have higher I.S than the standard and also have impact I.S against 1OQA breast cancer protein.

scholarly journals Synthesis and Structure–Activity Relationships of N-(4-Benzamidino)-Oxazolidinones–Potent and Selective Inhibitors of Kallikrein-Related Peptidase 6

2019 ◽  
Author(s):  
Elena De Vita ◽  
Niels Smits ◽  
Helma van den Hurk ◽  
Elizabeth M. Beck ◽  
Joanne Hewitt ◽  
...  
Keyword(s):  
Docking Studies ◽  
Rapid Progression ◽  
Single Digit ◽  
Aberrant Expression ◽  
The Family ◽  
Pharmacokinetic Properties ◽  
Related Enzyme ◽  
Hct116 Cells

Kallikrein-related peptidase 6 (KLK6) is a secreted serine protease that belongs to the family of tissue kallikreins. Aberrant expression of KLK6 has been found in different cancers and neurodegenerative diseases, and KLK6 is currently studied as a potential target in these pathologies. We report a novel series of KLK6 inhibitors discovered in a high-throughput screen within the European Lead Factory program. Structure-guided design based on docking studies enabled rapid progression of a hit cluster to inhibitors with improved potency, selectivity and pharmacokinetic properties. In particular, inhibitors <b>32</b> and<b> 34</b> have single digit nanomolar potency against KLK6, with over 25-fold and 100-fold selectivity, respectively, against the closely related enzyme trypsin. The most potent compound, <b>32</b>, effectively reduces KLK6-dependent invasion of HCT116 cells. The high potency in combination with good solubility and low clearance of <b>32</b> make it a good chemical probe for KLK6 target validation in vitro and potentially in vivo.

Recent Advancements in Docking Methodologies

Oncology ◽  
2017 ◽  
pp. 848-875
Author(s):  
Vijay Kumar Srivastav ◽  
Vineet Singh ◽  
Meena Tiwari
Keyword(s):  
Molecular Docking ◽  
Binding Free Energy ◽  
Binding Mode ◽  
Docking Studies ◽  
Protein Docking ◽  
Scoring Functions ◽  
Discovery Process ◽  
Ligand Complex ◽  
Small Molecule Databases ◽  
Homology Models

Nowadays molecular docking has become an important methodology in CADD (Computer-Aided Drug Design)-assisted drug discovery process. It is an important computational tool widely used to predict binding mode, binding affinity and binding free energy of a protein-ligand complex. The important factors responsible for accurate results in docking studies are correct binding site prediction, use of suitable small-molecule databases, consistent docking pose, high dock score with good MD (Molecular Dynamics), clarity whether the compound is an inhibitor or agonist, etc. However, still there are several limitations which make it difficult to obtain accurate results from docking studies. In this chapter, the main focus is on recent advancements in various aspects of molecular docking such as ligand sampling, protein flexibility, scoring functions, fragment docking, post-processing, docking into homology models and protein-protein docking.

Sign in / Sign up

Export Citation Format

Share Document