scholarly journals Podophyllotoxin and Quercetin in Silico Derivatives Docking Analysis with Cyclooxygenase-2 and Aminopeptidase-N

2021 ◽  
Author(s):  
A.E. Manukyan ◽  
A.A. Hovhannisyan
Keyword(s):  
In Silico ◽  
Biological Activities ◽  
Three Dimensional ◽  
Aminopeptidase N ◽  
Docking Analysis ◽  
Quercetin Derivatives ◽  
Pubchem Database ◽  
A Cell ◽  
Cox 2 ◽  
High Level

ABSTRACTThe cyclooxygenase (COX) enzymes are tumor markers, the inhibition of which can be used in the prevention and therapy of carcinogenesis. It was found that COX-2 IS considered as targets for tumor inhibition. Aminopeptidase N (APN) is a type II membrane-bound metalloprotease associated with cancer, being identified as a cell marker on the surface of malignant myeloid cells and reached a high level of expression in progressive tumors. In anticancer therapy, plant compounds are considered that can inhibit their activity. Modeling of the COX-2 and APN enzymes was carried out on the basis of molecular models of three-dimensional structures from the PDB database [PDB ID: 5f19, 4fyq] RCSB. For docking analysis, 3D ligand models were created using MarvinSketch based on the PubChem database [CID: 5280343, 5281654]. In silico experiments, for the first time, revealed the possible interaction and inhibition of COX-2 and APN by quercetin and quercetin derivatives. Aspirin and Marimastat were taken to compare the results. Possible biological activities and possible side effects of the ligands have been identified.

scholarly journals The Quercetin and Quercetin Derivatives Interaction With Cyclooxygenase-1 and Cyclooxygenase-2

2020 ◽  
Author(s):  
A.E. Manukyan ◽  
A.A. Hovhannisyan
Keyword(s):  
Biological Activities ◽  
Three Dimensional ◽  
Docking Analysis ◽  
Quercetin Derivatives ◽  
Cyclooxygenase 1 ◽  
Activity Modeling ◽  
Pubchem Database ◽  
Cox 2 ◽  
First Time ◽  
Cox 1

ABSTRACTThe cyclooxygenase (COX) enzymes are tumor markers, the inhibition of which can be used in the prevention and therapy of carcinogenesis. It was found that COX-1 and COX-2 are considered as targets for tumor inhibition. In anticancer therapy, plant compounds are considered that can inhibit their activity. Modeling of the COX-1 and COX-2 enzymes was carried out on the basis of molecular models of three-dimensional structures from the PDB database [PDB ID: 3KK6, 5f19] RCSB. For docking analysis, 3D ligand models were created using MarvinSketch based on the PubChem database [CID: 5280343, 5281654]. In silico experiments, for the first time, revealed the possible interaction and inhibition of COX-1 and COX-2 by quercetin and quercetin derivatives. Aspirin and Celecoxib [CID: 2244, 2662] were taken to compare the results. Possible biological activities and possible side effects of the ligands have been identified. It is noteworthy that Celecoxib is not active on the studied cell lines, while quercetin and quercetin derivatives are more active than Aspirin.

scholarly journals Preconditioned Cell Array Optimized for a Three-Dimensional Culture of Hepatocytes

2009 ◽  
Vol 18 (5-6) ◽  
pp. 677-682 ◽  
Author(s):  
Yoshitaka Miyamoto ◽  
Takeshi Ikeya ◽  
Shin Enosawa
Keyword(s):  
Cell Biology ◽  
Culture Medium ◽  
Biological Activities ◽  
Three Dimensional ◽  
Rat Hepatocytes ◽  
Cell Array ◽  
Cell Arrays ◽  
A Cell ◽  
Three Dimensional Culture ◽  
Hepatocyte Spheroids

Three-dimensional culture procedures have attracted attention in various fields of cell biology. A newly developed cell array assisted in the formation of hepatocyte spheroids by two innovations: 1) micropatterning by a hydrophilic polymer, and 2) the use of bovine carotid artery-derived HH cells as feeder cells. The former contributes to the standardization of the spheroid size and the latter to the maintenance of the spheroids. We created a way to provide a ready-to-use cell array by cryopreservation of an HH feeder cell cultured array. After inoculation of HH cells on the cell array, the culture medium was replaced by freezing medium containing dimethyl sulfoxide. Thereafter, the array was frozen and stored in a −80°C deep freezer. At the start of the hepatocyte culture, the cryopreserved HH cell array was thawed by adding warmed (37°C) culture medium. The morphology and biological activities of the cryopreserved HH cells were intact, as confirmed by phase contrast microscopy and functional staining with calcein and formazan. The rat hepatocytes formed perfect spheroids on the cryopreserved HH cell array without any differences from those on the freshly prepared HH cell array. The CYP3A drug metabolism activities of the hepatocytes were well maintained on the cryopreserved and fresh cell arrays. The present protocol greatly shortened the time and labor required to prepare a cell array for culturing hepatocytes.

scholarly journals In –silico molecular docking analysis of prodigiosin and cycloprodigiosin as COX-2 inhibitors

SpringerPlus ◽  
2013 ◽  
Vol 2 (1) ◽  
Author(s):  
Pabba Shiva Krishna ◽  
Kompally Vani ◽  
Metuku Ram Prasad ◽  
Burra Samatha ◽  
Nidadavolu Shesha Venkata Sathya Si Bindu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Docking Analysis ◽  
Cox 2 ◽  
In Silico Molecular Docking ◽  
Cox 2 Inhibitors ◽  
Molecular Docking Analysis

scholarly journals Synthesis, in silico molecular docking analysis, pharmacokinetic properties and evaluation of antibacterial and antioxidant activities of fluoroquinolines

BMC Chemistry ◽  
2022 ◽  
Vol 16 (1) ◽  
Author(s):  
Mona Fekadu ◽  
Digafie Zeleke ◽  
Bayan Abdi ◽  
Anuradha Guttula ◽  
Rajalakshmanan Eswaramoorthy ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Antioxidant Activities ◽  
Biological Activities ◽  
Dna Gyrase ◽  
Topoisomerase Iiα ◽  
Docking Analysis ◽  
E Coli ◽  
In Silico Molecular Docking ◽  
Molecular Docking Analysis

Abstract Background Quinolines have demonstrated various biological activities such as antimalarial, antibacterial and anticancer. Hence, compounds with such scaffold have been used as lead in drug development. This project is, therefore, aimed to synthesis and evaluates some biological activities of quinoline analogs. Methods 2-Chloro-7-fluoroquinoline-3-carbaldehydes were synthesized by the application of Vilsmeier–Haack reaction. The chlorine in the fluoroquinoline-3-carbaldehyde was replaced with various nucleophiles. The aldehyde functional group was also converted to carboxylic acid and imine groups using oxidizing agent and various amines, respectively. The structures of the compounds synthesized were characterized by spectroscopic methods. Disc diffusion and DPPH assays were used to evaluate the antibacterial and antioxidant activities, respectively. The in silico molecular docking analysis of the synthesized compounds were done using AutoDock Vina against E. coli DNA Gyrase B and human topoisomerase IIα. The drug likeness properties were assessed using SwissADME and PreADMET. Results Nine novel quinoline derivatives were synthesized in good yields. The in vitro antibacterial activity of the synthesized compounds was beyond 9.3 mm inhibition zone (IZ). Compounds 4, 5, 6, 7, 8, 10, 15, and 16 exhibited activity against E. coli, P. aeruginosa, S. aureus and S. pyogenes with IZ ranging from 7.3 ± 0.67 to 15.3 ± 0.33 mm at 200 μg/mL. Compound 9 displayed IZ against three of the bacterial strains except S. aureus. The IC50 for the radical scavenging activity of the synthesized compounds were from 5.31 to 16.71 μg/mL. The binding affinities of the synthesized compounds were from − 6.1 to − 7.2 kcal/mol against E. coli DNA gyrase B and − 6.8 to − 7.4 kcal/mol against human topoisomerase IIα. All of the synthesized compounds obeyed Lipinski’s rule of five without violation. Conclusion Compounds 4, 5, 6, 7, 8, 10, 15, and 16 displayed activity against Gram positive and Gram negative bacterial strains indicating that these compounds might be used as broad spectrum bactericidal activity. Compound 8 (13.6 ± 0.22 mm) showed better IZ against P. aeruginosa compared with ciprofloxacin (10.0 ± 0.45 mm) demonstrating the potential of this compound as antibacterial agent against this strain. Compounds 5, 6, 7, 8, 9 and 10 showed comparable binding affinities in their in silico molecular docking analysis against E. coli DNA gyrase B. All of the synthesized compounds also obeyed Lipinski’s rule of five without violation which suggests these compounds as antibacterial agents for further study. Compounds 7 and 8 were proved to be a very potent radical scavenger with IC50 values of 5.31 and 5.41 μg/mL, respectively. Compound 5, 6, 8, 10 and 16 had comparable binding affinity against human topoisomerase IIα suggesting these compounds as a possible candidate for anticancer drugs.

scholarly journals Assessment of the Pharmacological Properties and Phytochemical Profile of Bruguiera gymnorhiza (L.) Lam Using In Vitro Studies, In Silico Docking, and Multivariate Analysis

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 731 ◽  
Author(s):  
Nabeelah Bibi Sadeer ◽  
Kouadio Ibrahime Sinan ◽  
Zoltán Cziáky ◽  
József Jekő ◽  
Gokhan Zengin ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
In Silico ◽  
Biological Activities ◽  
Radical Scavenging ◽  
Total Phenolic ◽  
Docking Analysis ◽  
In Silico Docking ◽  
Bruguiera Gymnorhiza ◽  
Phytochemical Profile

Bruguiera gymnorhiza (L.) Lam. is claimed to effectively manage a number of ailments including diabetes and associated complications. Nonetheless, no attempt has been made to delineate its pharmacological propensities and phytochemical profile. This study was designed to appraise the antioxidant and enzymatic inhibitory properties relevant to the management of diabetes mellitus, obesity, and neurodegenerative and skin disorders. A combination of colorimetric assays and ultra-high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS) were applied for the phytochemical screening of leaf, root, twig, and fruit extracts (methanol and ethyl acetate). In vitro antioxidant evaluations were via radical scavenging abilities (DPPH, ABTS), reducing potential (FRAP, CUPRAC), chelating power, and total antioxidant capacity (phosphomolybdenum). Seven key metabolic enzymes (α-amylase, α-glucosidase, tyrosinase, elastase, lipase, AChE, and BChE) were targeted to determine the inhibitory effects. Multivariate and in silico docking analysis were performed on collected data. Methanolic fruit extract yielded the highest total phenolic, tannin, and triterpenoid contents (174.18 ± 4.27 mg GAE/g, 176.24 ± 3.10 mg CE/g, 63.11 ± 3.27 mg OAE/g, respectively); significantly depressed tyrosinase, elastase, and α-amylase activities (155.35 ± 0.29 mg KAE/g, 4.56 ± 0.10 mg CAE/g, 1.00 ± 0.05 mmol ACAE/g, accordingly); and harboured the most potent antioxidant capacities with DPPH, CUPRAC, FRAP (492.62 ± 5.31, 961.46 ± 11.18, 552.49 ± 8.71 mg TE/g, respectively), and phosphomolybdenum (4.17 ± 0.31 mmol TE/g) assays. Multivariate analysis suggested that the type of solvents used influenced the biological activities more compared to plant parts. Docking analysis showed that azelaic acid binds with tyrosinase by Van der Waals and conventional hydrogen bonds. We anticipate that the present study may establish baseline data on this halophyte that could open new avenues for the development of biomedicine.

Guided surgery with 3D printed device: a case report

2020 ◽  
Author(s):  
Michelle Carvalho de Sales ◽  
Rafael Maluza Flores ◽  
Julianny da Silva Guimaraes ◽  
Gustavo Vargas da Silva Salomao ◽  
Tamara Kerber Tedesco ◽  
...  
Keyword(s):  
Operating Time ◽  
Three Dimensional ◽  
Conventional Technique ◽  
Cervical Region ◽  
Mean Deviation ◽  
Apical Region ◽  
Virtual Planning ◽  
Surgical Guide ◽  
Surgical Guides ◽  
High Level

Dental surgeons need in-depth knowledge of the bone tissue status and gingival morphology of atrophic maxillae. The aim of this study is to describe preoperative virtual planning of placement of five implants and to compare the plan with the actual surgical results. Three-dimensional planning of rehabilitation using software programs enables surgical guides to be specially designed for the implant site and manufactured using 3D printing. A patient with five teeth missing was selected for this study. The patient’s maxillary region was scanned with CBCT and a cast model was produced. After virtual planning using ImplantViewer, five implants were placed using a printed surgical guide. Two weeks after the surgical procedure, the patient underwent another CBCT scan of the maxilla. Statistically significant differences were detected between the virtually planned positions and the actual positions of the implants, with a mean deviation of 0.36 mm in the cervical region and 0.7 mm in the apical region. The surgical technique used enables more accurate procedures when compared to the conventional technique. Implants can be better positioned, with a high level of predictability, reducing both operating time and patient discomfort.

In the Quest for a Stable Triplet State in Small Polyaromatic Hydrocarbons : An In-Silico Tool for Rational Design and Prediction

2019 ◽  
Author(s):  
Madhumita Rano ◽  
Sumanta K Ghosh ◽  
Debashree Ghosh
Keyword(s):  
Triplet State ◽  
Small Molecules ◽  
In Silico ◽  
Qualitative Agreement ◽  
Rational Design ◽  
Polyaromatic Hydrocarbons ◽  
Spin Hamiltonian ◽  
Spin Frustration ◽  
Computationally Efficient ◽  
High Level

<div>Combining the roles of spin frustration and geometry of odd and even numbered rings in polyaromatic hydrocarbons (PAHs), we design small molecules that show exceedingly small singlet-triplet gaps and stable triplet ground states. Furthermore, a computationally efficient protocol with a model spin Hamiltonian is shown to be capable of qualitative agreement with respect to high level multireference calculations and therefore, can be used for fast molecular discovery and screening.</div>

In Silico Identification and Molecular Characterization of Extracellular Cathepsin L Proteases from Giardia duodenalis

2020 ◽  
Vol 17 (4) ◽  
pp. 342-351
Author(s):  
Sergio A. Durán-Pérez ◽  
José G. Rendón-Maldonado ◽  
Lucio de Jesús Hernandez-Diaz ◽  
Annete I. Apodaca-Medina ◽  
Maribel Jiménez-Edeza ◽  
...  
Keyword(s):  
In Silico ◽  
Cathepsin L ◽  
Three Dimensional ◽  
Giardia Duodenalis ◽  
Evolutionary Genetics ◽  
Extracellular Proteins ◽  
In Silico Identification ◽  
Dimensional Models ◽  
Three Dimensional Models

Background: The protozoan Giardia duodenalis, which causes giardiasis, is an intestinal parasite that commonly affects humans, mainly pre-school children. Although there are asymptomatic cases, the main clinical features are chronic and acute diarrhea, nausea, abdominal pain, and malabsorption syndrome. Little is currently known about the virulence of the parasite, but some cases of chronic gastrointestinal alterations post-infection have been reported even when the infection was asymptomatic, suggesting that the cathepsin L proteases of the parasite may be involved in the damage at the level of the gastrointestinal mucosa. Objective: The aim of this study was the in silico identification and characterization of extracellular cathepsin L proteases in the proteome of G. duodenalis. Methods: The NP_001903 sequence of cathepsin L protease from Homo sapienswas searched against the Giardia duodenalisproteome. The subcellular localization of Giardia duodenaliscathepsin L proteases was performed in the DeepLoc-1.0 server. The construction of a phylogenetic tree of the extracellular proteins was carried out using the Molecular Evolutionary Genetics Analysis software (MEGA X). The Robetta server was used for the construction of the three-dimensional models. The search for possible inhibitors of the extracellular cathepsin L proteases of Giardia duodenaliswas performed by entering the three-dimensional structures in the FINDSITEcomb drug discovery tool. Results: Based on the amino acid sequence of cathepsin L from Homo sapiens, 8 protein sequences were identified that have in their modular structure the Pept_C1A domain characteristic of cathepsins and two of these proteins (XP_001704423 and XP_001704424) are located extracellularly. Threedimensional models were designed for both extracellular proteins and several inhibitory ligands with a score greater than 0.9 were identified. In vitrostudies are required to corroborate if these two extracellular proteins play a role in the virulence of Giardia duodenalisand to discover ligands that may be useful as therapeutic targets that interfere in the mechanism of pathogenesis generated by the parasite. Conclusion: In silicoanalysis identified two proteins in the Giardia duodenalisprotein repertoire whose characteristics allowed them to be classified as cathepsin L proteases, which may be secreted into the extracellular medium to act as virulence factors. Three-dimensional models of both proteins allowed the identification of inhibitory ligands with a high score. The results suggest that administration of those compounds might be used to block the endopeptidase activity of the extracellular cathepsin L proteases, interfering with the mechanisms of pathogenesis of the protozoan parasite Giardia duodenalis.

Design, Synthesis, Characterization and in silico molecular docking studies and in vivo anti-inflammatory Activity of Pyrazoline clubbed Thiazolinone Derivatives

2020 ◽  
Vol 17 ◽  
Author(s):  
Deepak Kumar Singh ◽  
Mayank Kulshreshtha ◽  
Yogesh Kumar ◽  
Pooja A Chawla ◽  
Akash Ved ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Biological Activities ◽  
Inflammatory Activity ◽  
Standard Drug ◽  
Docking Score ◽  
Chemical Structures ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

Background: The pyrazolines give the reactions of aliphatic derivatives, resembling unsaturated compounds in their behavior towards permanganate and nascent hydrogen. This nucleus has been associated with various biological activities including inflammatory. Thiazolinone is a heterocyclic compound that contains both sulfur and nitrogen atom with a carbonyl group in their structure.Thiazolinone and their derivatives have attracted continuing interest because of their various biological activities, such as anti-inflammatory, antimicrobial, anti-proliferative, antiviral, anticonvulsant etc. The aim of the research was to club pyrazoline nucleus with thiazolinone in order to have significantanti-inflammatory activity. The synthesized compounds were chemically characterized for the establishment of their chemical structures and to evaluate as anti-inflammatory agent. Method: In the present work, eight derivatives of substituted pyrazoline (PT1-PT8) were synthesized by a three step reaction.The compounds were subjected to spectral analysis by Infrared, Mass and Nuclear magnetic resonance spectroscopy and elemental analysis data. All the synthesized were evaluated for their in vivo anti-inflammatory activity. The synthesized derivatives were evaluated for their affinity towards target COX-1 and COX-2, using indomethacin as the reference compound molecular docking visualization through AutoDock Vina. Results: Compounds PT-1, PT-3, PT-4 and PT-8 exhibited significant anti-inflammatory activity at 3rd hour being 50.7%, 54.3%, 52.3% and 57% respectively closer to that of the standard drug indomethacin (61.9%).From selected anti-inflammatory targets, the synthesized derivatives exhibited better interaction with COX-1 and COX-2 receptor, where indomethacin showed docking score of -6.5 kJ/mol, compound PT-1 exhibited highest docking score of -9.1 kJ/mol for COX-1 and compound PT-8 having docking score of 9.4 kJ/mol for COX-2. Conclusion: It was concluded that synthesized derivatives have more interaction with COX-2 receptors in comparison to the COX-1 receptors because the docking score with COX-2 receptors were very good. It is concluded that the synthesized derivatives (PT-1 to PT-8) are potent COX-2 inhibitors.

α-Glucosidase Inhibition, Antioxidant and Docking Studies of Hydroxycoumarins and their Mono and Bis O-alkylated/acetylated Analogs

2018 ◽  
Vol 15 (2) ◽  
pp. 127-135 ◽  
Author(s):  
Parvesh Singh ◽  
Nomandla Ngcoya ◽  
Ramgopal Mopuri ◽  
Nagaraju Kerru ◽  
Neha Manhas ◽  
...  
Keyword(s):  
In Silico ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Catalytic Site ◽  
Docking Simulations ◽  
In Silico Docking ◽  
Anti Oxidant

Background: Diabetes Mellitus (DM) is a complex metabolic disease illustrated by abnormally high levels of plasma glucose or hyperglycaemia. Accordingly, several α-glucosidase inhibitors have been developed for the treatment of diabetes and other degenerative disorders. While, a coumarin ring has the privilege to represent numerous natural and synthetic compounds with a wide spectrum of biological activities e.g. anti-cancer, anti-HIV, anti-viral, anti-malarial, anti-microbial, anti-convulsant, anti-hypertensive properties. Besides this, coumarins have also shown potential to inhibit α-glucosidase leading to a generation of new promising antidiabetic agents. However, the testing of O-substituted coumarins for α-glucosidase inhibition has evaded the attention of medicinal chemists. Methods: For O-alkylation/acetylation reactions, the hydroxyl coumarins (A-B) initially activated by K2CO3 in dry DMF were reacted with variedly substituted haloalkanes at room temperature under nitrogen. The synthesized compounds were tested for their α-glucosidase (from Saccharomyces cerevisiae) inhibitory activity and anti-oxidant activity using DPPH radical scavenging activity. In silico docking simulations were conducted using CDocker module in DS (Accelrys) to explore the binding modes of the representative compounds in the catalytic site of α-glucosidase. Results: All the coumarin analogues (A1, B1, A2-A10, B2-B8) including their precursors (A-B) were evaluated for their in vitro α-glucosidase inhibition using acarbose as a standard inhibitor. All the mono O-alkylated coumarins (except A1) showed significant (p <0.05) α-glucosidase inhibition relative to the hydroxyl coumarin (A) with IC50 values ranging between 11.084±0.117 to 145.24± 29.22 µg/mL. Compound 7-(benzyloxy)-4, 5-dimethyl-2H-chromen-2-one (A9) bearing a benzyl group (Ph-CH2-) at position 7 showed a remarkable (p <0.05) increase in the activity (IC50 = 11.084±0.117 µg/mL), almost four-fold more than acarbose (IC50 = 40.578±5.999 µg/mL). The introduction of –NO2 group dramatically improved the anti-oxidant activity of coumarin, while the O-alkylation/acetylation decreased the activity. Conclusion: The present study describes the synthesis of functionalized coumarins and their evaluation for α-glucosidase inhibition and antioxidant activity under in vitro conditions. Based on IC50 data, the mono O-alkylated coumarins were observed to be stronger inhibitors of α-glucosidase with respect to their bis O-alkylated analogues. Coumarin (A9) bearing O-benzyloxy group displayed the strongest α-glucosidase inhibition, even higher than the standard inhibitor acarbose. The coumarin (A10) bearing –NO2 group showed the highest anti-oxidant activity amongst the synthesized compounds, almost comparable to the ascorbic acid. Finally, in silico docking simulations revealed the role of hydrogen bonding and hydrophobic forces in locking the compounds in catalytic site of α-glucosidase.

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