Appraisal of the role of In silico Methods in Pyrazole based drug design

2020 ◽  
Vol 20 ◽  
Author(s):  
Smriti Sharma ◽  
Vinayak Bhatia
Keyword(s):  
Drug Design ◽  
In Silico ◽  
Md Simulations ◽  
Quantitative Structure Activity Relationship ◽  
Field Analysis ◽  
Computational Techniques ◽  
Neuroprotective Drugs ◽  
Pharmacological Potential ◽  
Available Information ◽  
Anti Fungal

: Pyrazole and its derivatives are a pharmacologically significant active scaffold that have innumerable physiological and pharmacological activities. They can be very good targets for the discovery of novel anti-bacterial, anticancer, anti-inflammatory, anti-fungal, anti-tubercular, antiviral, antioxidant, antidepressant, anti-convulsant and neuroprotective drugs. This review focuses on the importance of in silico manipulations of pyrazole and its derivatives for medicinal chemistry. The authors have discussed currently available information on the use of computational techniques like molecular docking, structure-based virtual screening (SBVS), molecular dynamics (MD) simulations, quantitative structure activity relationship (QSAR), comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) to drug design using pyrazole moieties. Pyrazole based drug design is mainly dependent on the integration of experimental and computational approaches. The authors feel that more studies need to be done to fully explore the pharmacological potential of the pyrazole moiety and in silico method can be of great help.

Drug Design of GLP-1 Receptor Agonists: Importance of In silico Methods

2020 ◽  
Vol 26 ◽  
Author(s):  
Smriti Sharma ◽  
Vinayak Bhatia
Keyword(s):  
Drug Design ◽  
In Silico ◽  
Experimental Studies ◽  
Receptor Agonists ◽  
Drug Molecules ◽  
Glucagon Like Peptide 1 ◽  
Long Acting ◽  
Almost All ◽  
Available Information ◽  
Novel Drug

: Drug design based on degradation-resistant, long-acting Glucagon-like peptide-1 receptor (GLP-1R) agonists for treating type 2 diabetes is attracting lot of attention. Here, the authors have examined in detail how in silico drug design is aiding in developing novel GLP-1 receptor agonist drugs. Their pharmacotherapy and adverse effects have also been summarized. After the analysis of currently available information on this topic, the authors feel that in silico method is a great auxiliary tool in almost all the experimental studies on GLP-1 receptors and is highly efficient in identifying novel drug molecules that can act as GLP-1 receptor agonists.

Design, Synthesis and Biological Evaluation of Novel Fentanyl Analogues as Agonist of μ-Opioid Receptor

2012 ◽  
Vol 217-219 ◽  
pp. 937-940 ◽  
Author(s):  
Ming Liu ◽  
Wen Xiang Hu
Keyword(s):  
Opioid Receptor ◽  
Rational Design ◽  
Biological Activities ◽  
Md Simulations ◽  
Quantitative Structure Activity Relationship ◽  
Biological Evaluation ◽  
Field Analysis ◽  
Qsar Studies ◽  
Μ Opioid Receptor ◽  
Fentanyl Analogues

The research of our group focus on the studies of fentanyl analogues, which have potent analgesics free of side effects. Firstly, homology modeling, molecular docking, pharmacophore mapping, comparative molecular force field analysis(CoMFA), quantitative structure activity relationship(QSAR) studies and molecular dynamics(MD) simulations are applied in our research to gain a better understanding of the molecular interactions between the new fentanyl analogues(FA) and μ-opioid receptor(MOR), which provides a more rational design of targeting drugs. Secondly, chemical synthesis of novel compounds have been carried out successfully and their sturctures were confirmed by Nuclear Magnetic Resonance(NMR) and Mass Spectrom(MS). Lastly, in view of the functional roles of higher selectivity and affinity, the evaluation of the biological activities is ongoing.

Rational Drug Design Approach of Receptor Tyrosine Kinase Type III Inhibitors

2020 ◽  
Vol 26 (42) ◽  
pp. 7623-7640 ◽  
Author(s):  
Cheolhee Kim ◽  
Eunae Kim
Keyword(s):  
Drug Design ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Synergistic Effects ◽  
Rational Drug Design ◽  
Computational Techniques ◽  
Biological Targets ◽  
Type Iii ◽  
Theoretical Approaches ◽  
Rational Drug

: Rational drug design is accomplished through the complementary use of structural biology and computational biology of biological macromolecules involved in disease pathology. Most of the known theoretical approaches for drug design are based on knowledge of the biological targets to which the drug binds. This approach can be used to design drug molecules that restore the balance of the signaling pathway by inhibiting or stimulating biological targets by molecular modeling procedures as well as by molecular dynamics simulations. Type III receptor tyrosine kinase affects most of the fundamental cellular processes including cell cycle, cell migration, cell metabolism, and survival, as well as cell proliferation and differentiation. Many inhibitors of successful rational drug design show that some computational techniques can be combined to achieve synergistic effects.

Phytochemicals for drug discovery in Alzheimer’s disease: In silico Advances

2020 ◽  
Vol 26 ◽  
Author(s):  
Smriti Sharma ◽  
Vinayak Bhatia
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Design ◽  
In Silico ◽  
Drug Targets ◽  
Development Process ◽  
Phytochemical Analysis ◽  
Computational Drug Design ◽  
Novel Drugs ◽  
Game Changer

: The search for novel drugs that can prevent or control Alzheimer’s disease has attracted lot of attention from researchers across the globe. Phytochemicals are increasingly being used to provide scaffolds to design drugs for AD. In silico techniques, have proven to be a game-changer in this drug design and development process. In this review, the authors have focussed on current advances in the field of in silico medicine, applied to phytochemicals, to discover novel drugs to prevent or cure AD. After giving a brief context of the etiology and available drug targets for AD, authors have discussed the latest advances and techniques in computational drug design of AD from phytochemicals. Some of the prototypical studies in this area are discussed in detail. In silico phytochemical analysis is a tool of choice for researchers all across the globe and helps integrate chemical biology with drug design.

Prediction of Drug-Drug Interactions Related to Inhibition or Induction of Drug-Metabolizing Enzymes

2019 ◽  
Vol 19 (5) ◽  
pp. 319-336 ◽  
Author(s):  
Alexander V. Dmitriev ◽  
Alexey A. Lagunin ◽  
Dmitry А. Karasev ◽  
Anastasia V. Rudik ◽  
Pavel V. Pogodin ◽  
...  
Keyword(s):  
In Silico ◽  
Computational Models ◽  
Field Analysis ◽  
Pharmaceutical Chemistry ◽  
Sources Of Information ◽  
Metabolizing Enzymes ◽  
Physiologically Based Pharmacokinetic ◽  
Pharmacophore Models ◽  
Drug Metabolising Enzymes ◽  
In Silico Methods

Drug-drug interaction (DDI) is the phenomenon of alteration of the pharmacological activity of a drug(s) when another drug(s) is co-administered in cases of so-called polypharmacy. There are three types of DDIs: pharmacokinetic (PK), pharmacodynamic, and pharmaceutical. PK is the most frequent type of DDI, which often appears as a result of the inhibition or induction of drug-metabolising enzymes (DME). In this review, we summarise in silico methods that may be applied for the prediction of the inhibition or induction of DMEs and describe appropriate computational methods for DDI prediction, showing the current situation and perspectives of these approaches in medicinal and pharmaceutical chemistry. We review sources of information on DDI, which can be used in pharmaceutical investigations and medicinal practice and/or for the creation of computational models. The problem of the inaccuracy and redundancy of these data are discussed. We provide information on the state-of-the-art physiologically- based pharmacokinetic modelling (PBPK) approaches and DME-based in silico methods. In the section on ligand-based methods, we describe pharmacophore models, molecular field analysis, quantitative structure-activity relationships (QSAR), and similarity analysis applied to the prediction of DDI related to the inhibition or induction of DME. In conclusion, we discuss the problems of DDI severity assessment, mention factors that influence severity, and highlight the issues, perspectives and practical using of in silico methods.

In Silico and in Vitro Evaluation of Deamidation Effects on the Stability of the Fusion Toxin DAB389IL-2

2019 ◽  
Vol 16 (4) ◽  
pp. 307-313 ◽  
Author(s):  
Nasrin Zarkar ◽  
Mohammad Ali Nasiri Khalili ◽  
Fathollah Ahmadpour ◽  
Sirus Khodadadi ◽  
Mehdi Zeinoddini
Keyword(s):  
In Silico ◽  
Catalytic Domain ◽  
Md Simulations ◽  
Special Importance ◽  
Native Form ◽  
Vitro Experiment ◽  
In Vitro Experiment ◽  
Pharmaceutical Protein ◽  
The Stability

Background: DAB389IL-2 (Denileukin diftitox) as an immunotoxin is a targeted pharmaceutical protein and is the first immunotoxin approved by FDA. It is used for the treatment of various kinds of cancer such as CTCL lymphoma, melanoma, and Leukemia but among all of these, treatment of CTCL has special importance. DAB389IL-2 consists of two distinct parts; the catalytic domain of Diphtheria Toxin (DT) that genetically fused to the whole IL-2. Deamidation is the most important reaction for chemical instability of proteins occurs during manufacture and storage. Deamidation of asparagine residues occurs at a higher rate than glutamine residues. The structure of proteins, temperature and pH are the most important factors that influence the rate of deamidation. Methods: Since there is not any information about deamidation of DAB389IL-2, we studied in silico deamidation by Molecular Dynamic (MD) simulations using GROMACS software. The 3D model of fusion protein DAB389IL-2 was used as a template for deamidation. Then, the stability of deamidated and native form of the drug was calculated. Results: The results of MD simulations were showed that the deamidated form of DAB389IL-2 is more unstable than the normal form. Also, deamidation was carried by incubating DAB389IL-2, 0.3 mg/ml in ammonium hydrogen carbonate for 24 h at 37o C in order to in vitro experiment. Conclusion: The results of in vitro experiment were confirmed outcomes of in silico study. In silico and in vitro experiments were demonstrated that DAB389IL-2 is unstable in deamidated form.

3D-QSAR Studies of S-DABO Derivatives as Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors

2019 ◽  
Vol 16 (8) ◽  
pp. 868-881
Author(s):  
Yueping Wang ◽  
Jie Chang ◽  
Jiangyuan Wang ◽  
Peng Zhong ◽  
Yufang Zhang ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Three Dimensional ◽  
Predictive Ability ◽  
3D Qsar ◽  
Binding Mode ◽  
Quantitative Structure Activity Relationship ◽  
Field Analysis ◽  
Reverse Transcriptase Inhibitors ◽  
Qsar Studies ◽  
Hiv 1

Background: S-dihydro-alkyloxy-benzyl-oxopyrimidines (S-DABOs) as non-nucleoside reverse transcriptase inhibitors have received considerable attention during the last decade due to their high potency against HIV-1. Methods: In this study, three-dimensional quantitative structure-activity relationship (3D-QSAR) of a series of 38 S-DABO analogues developed in our lab was studied using Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA). The Docking/MMFF94s computational protocol based on the co-crystallized complex (PDB ID: 1RT2) was used to determine the most probable binding mode and to obtain reliable conformations for molecular alignment. Statistically significant CoMFA (q2=0.766 and r2=0.949) and CoMSIA (q2=0.827 and r2=0.974) models were generated using the training set of 30 compounds on the basis of hybrid docking-based and ligand-based alignment. Results: The predictive ability of CoMFA and CoMSIA models was further validated using a test set of eight compounds with predictive r2 pred values of 0.843 and 0.723, respectively. Conclusion: The information obtained from the 3D contour maps can be used in designing new SDABO derivatives with improved HIV-1 inhibitory activity.

scholarly journals Effect of hydrophobically modified PEO polymers (PEO-dodecyl) on oil/water microemulsion properties: in vitro and in silico investigations

RSC Advances ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 7059-7069
Author(s):  
M. Khatouri ◽  
R. Ahfir ◽  
M. Lemaalam ◽  
S. El Khaoui ◽  
A. Derouiche ◽  
...  
Keyword(s):  
Integral Equations ◽  
In Silico ◽  
Md Simulations ◽  
Hydrophobically Modified ◽  
Oil Water

In this work, we study the effect of grafted PEO-dodecyl co-polymers on the decane/water microemulsions properties. For this purpose, we combined the MD simulations, the OZ integral equations resolved using the HNC closure, and SANS experiments.

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