Computational Drug Designing and Prediction Of Important Parameters Using in silico Methods- A Review

2019 ◽  
Vol 15 (5) ◽  
pp. 384-397
Author(s):  
Tahmeena Khan ◽  
Alfred J. Lawrence ◽  
Iqbal Azad ◽  
Saman Raza ◽  
Seema Joshi ◽  
...  
Keyword(s):  
In Silico ◽  
Docking Studies ◽  
Drug Uptake ◽  
Drug Candidate ◽  
Potential Drug ◽  
Toxicological Assessment ◽  
Biological Targets ◽  
In Silico Studies ◽  
Drug Designing

Background:: Computational or in silico studies are undertaken to assess the drug like properties of lead compounds. These studies help in fast prediction of relevant properties. Objective: : Through this review, an effort is made to encapsulate some of the important parameters which should be met by a compound for it to be considered as a potential drug candidate along with an overview of automated softwares which can be used for making various predictions. Methods:: Drug uptake, its absorption, evacuation and associated hazardous effects are important factors for consideration in drug designing and should be known in early stages of drug development. Several important physicochemical properties like molecular weight, polar surface area (PSA), molecular flexibility etc. have to be taken into consideration in drug designing. Toxicological assessment is another important aspect of drug discovery which predicts the safety and adverse effects of a drug. Results: : Additionally, bioactivity scores of probable drug leads against various human receptors can also be predicted to evaluate the probability of them to act as a potential drug candidate. The in vivo biological targets of a molecule can also be efficiently predicted by molecular docking studies. Conclusion:: Some important software like iGEMDOCK, AutoDock, OSIRIS property explorer, Molinspiration, MetaPrint2D, admetSAR and their working methodology and principle of working have been summarized in this review.

In-silico Studies of Isolated Phytoalkaloid Against Lipoxygenase: Study Based on Possible Correlation

2018 ◽  
Vol 21 (3) ◽  
pp. 215-221
Author(s):  
Haroon Khan ◽  
Muhammad Zafar ◽  
Helena Den-Haan ◽  
Horacio Perez-Sanchez ◽  
Mohammad Amjad Kamal
Keyword(s):  
In Silico ◽  
Docking Studies ◽  
In Vivo Studies ◽  
In Vitro Assays ◽  
Chronic Obstructive ◽  
Lipoxygenase Inhibitors ◽  
Lipoxygenase Inhibition ◽  
In Silico Studies

Aim and Objective: Lipoxygenase (LOX) enzymes play an important role in the pathophysiology of several inflammatory and allergic diseases including bronchial asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, rheumatoid arthritis and chronic obstructive pulmonary disease. Inhibitors of the LOX are believed to be an ideal approach in the treatment of diseases caused by its over-expression. In this regard, several synthetic and natural agents are under investigation worldwide. Alkaloids are the most thoroughly investigated class of natural compounds with outstanding past in clinically useful drugs. In this article, we have discussed various alkaloids of plant origin that have already shown lipoxygenase inhibition in-vitro with possible correlation in in silico studies. Materials and Methods: Molecular docking studies were performed using MOE (Molecular Operating Environment) software. Among the ten reported LOX alkaloids inhibitors, derived from plant, compounds 4, 2, 3 and 1 showed excellent docking scores and receptor sensitivity. Result and Conclusion: These compounds already exhibited in vitro lipoxygenase inhibition and the MOE results strongly correlated with the experimental results. On the basis of these in vitro assays and computer aided results, we suggest that these compounds need further detail in vivo studies and clinical trial for the discovery of new more effective and safe lipoxygenase inhibitors. In conclusion, these results might be useful in the design of new and potential lipoxygenase (LOX) inhibitors.

scholarly journals Inhibition of Phosphodiesterase 5 Enzyme by Pterine- 6 Carboxylic Acid from Baphia nitida –Related to Erectile Dysfunction: Computational Kinetic

2020 ◽  
pp. 49-55
Author(s):  
Wopara, Iheanyichukwu ◽  
S. K. Mobisson ◽  
Egelege Aziemeola Pius ◽  
A. A. Uwakwe ◽  
M. O. Wegwu
Keyword(s):  
Erectile Dysfunction ◽  
Carboxylic Acid ◽  
Active Site ◽  
In Silico ◽  
Binding Pocket ◽  
Docking Studies ◽  
Drug Candidate ◽  
In Silico Docking ◽  
In Silico Studies ◽  
Phosphodiesterase 5

Treatment of erectile dysfunction is associated with inhibition of Phosphodiesterase 5 enzyme. This study deals with the evaluation of Pterin-6-carboxylic acid inhibitory activity on phosphodiesterase 5 (PDB ID: 4OEW) using in silico docking studies. Pterin-6-carboxylic acid from Baphia nitida was isolated using GC-MS and docked into PDE5 active site. The docking result showed that pterin-6-carboxylic acid bind to the active site of phosphodiesterase 5 with the binding energy value of -7.1 and 2.05A° - 2.23A° when compared with other compound found in the plant. Moreso, docking analysis with the ligand identified specific residues such as: Ile 778, Phe 820, Gln 817, Ser 815 and Gln 775 within the binding pocket which played an important role in the ligand binding affinity to the protein. Result from our In silico studies hypothesized that pterin-6-carboxylic acid can be an inhibitory agent for PDE5 protein which could be a potential drug candidate for the treatment of erectile dysfunction.

New Benzodioxole-based Pyrazoline Derivatives: Synthesis and Anticandidal, In silico ADME, Molecular Docking Studies

2018 ◽  
Vol 16 (1) ◽  
pp. 82-92 ◽  
Author(s):  
Ahmet Özdemir ◽  
Belgin Sever ◽  
Mehlika Dilek Altıntop
Keyword(s):  
In Silico ◽  
Fungal Infections ◽  
Computational Study ◽  
Docking Studies ◽  
In Vivo Studies ◽  
Heme Group ◽  
In Silico Studies ◽  
Nih 3T3

Background: Azoles are commonly used in the treatment and prevention of fungal infections. They suppress fungal growth by acting on the heme group of lanosterol 14α-demethylase enzyme (CYP51), thus blocking the biosynthesis of ergosterol. </P><P> Objectives: Due to the importance of pyrazolines in the field of antifungal drug design, we aimed to design and synthesize new pyrazoline-based anticandidal agents. Methods: New pyrazoline derivatives were synthesized via the reaction of 1-(chloroacetyl)-3-(2- thienyl)-5-(1,3-benzodioxol-5-yl)-2-pyrazoline with aryl thiols. These compounds were evaluated for their in vitro antifungal effects on Candida species. Docking studies were performed to predict the affinity of the most effective anticandidal agents to substrate binding site of CYP51. Furthermore, MTT assay was performed to determine the cytotoxic effects of the compounds on NIH/3T3 mouse embryonic fibroblast cell line. A computational study for the prediction of ADME properties of all compounds was also carried out. Results: Compounds 5, 8, 10 and 12 were found as the most potent anticandidal agents against Candida albicans and Candida glabrata in this series with the same MIC values of ketoconazole and they also exhibited low toxicity against NIH/3T3 cells. Docking results indicated that all these compounds showed good binding affinity into the active site of CYP51. In particular, chloro substituted compounds 8 and 12 bind to CYP51 through direct coordination with the heme group. According to in silico studies, compound 8 only violated one parameter of Lipinski’s rule of five, making it a potential orally bioavailable agent. Conclusion: Compound 8 was defined as a promising candidate for further in vitro and in vivo studies.

scholarly journals In Silico Analysis and Molecular Docking Studies of Plumbagin and Piperine Ligands as Potential Inhibitors of Alpha-Glucosidase Receptor

2020 ◽  
Vol 11 (2) ◽  
pp. 9629-9637
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
Docking Studies ◽  
The Body ◽  
Insufficient Amount ◽  
In Silico Studies ◽  
Optimization Simulation ◽  
Alpha Glucosidase

In ’today’s generation, Diabetes mellitus is a very common lifestyle-based disease in which an insufficient amount of insulin is produced, which results in a rise of glucose level in the body with frequent urination and patient feels thirsty and hungry. In our present work, we have used the alpha-glucosidase receptor against the natural plant product as a ligand for docking studies. For this in silico studies, various online tools, databases, and software were used. The proposed approaches were PDB, Molinspiration, Chemsketch, PyRx software, and many more. The binding scores were retrieved by PyRx software and no tumorigenicity, mutagenicity was there, and all parameters were in the desired range. The compounds used as ligands have shown energy minimization up to -6.7 to -8.7 kcal and can be further used as optimization, simulation, and in vitro and in vivo experimental validation.

scholarly journals Design, Synthesis and Antidiabetic Activity of Novel Sulfamoyl Benzamide Derivatives as Glucokinase Activators

2018 ◽  
Vol 6 (2) ◽  
pp. 115-124
Author(s):  
Ajmer Singh Grewal ◽  
Kapil Sharma ◽  
Sukhbir Singh ◽  
Vikramjeet Singh ◽  
Deepti Pandita ◽  
...  
Keyword(s):  
In Silico ◽  
Animal Studies ◽  
Docking Studies ◽  
Antidiabetic Activity ◽  
Allosteric Site ◽  
In Silico Docking ◽  
Glucokinase Activators ◽  
In Silico Studies ◽  
Benzamide Derivatives

The present work has been planned to design, synthesize and evaluate the antidiabetic potential of a series of sulfamoyl benzamide derivatives as potential glucokinase (GK) activators. A new series of sulfamoyl benzamide derivatives was synthesized starting from 3-nitrobenzoic acid and characterized. In silico docking studies were performed to determine the binding interactions for the best fit conformations in the allosteric site of GK enzyme. Based on the results of in silico studies, the selected molecules were tested for their antidiabetic activity in animal studies (alloxan induced diabetic animal model). Compound 7 exhibited highest antidiabetic activity in animal studies. The results of in vivo antidiabetic activity studies were found to be in parallel to that of docking studies. These newly synthesized sulfamoyl benzamide derivatives thus can be treated as the initial hits for the development of novel, safe, effective and orally bioavailable GK activators as therapeutic agents for the treatment of type 2 diabetes.

scholarly journals In-silico studies of Riparin B in the design of drugs: Physicochemical, pharmacokinetic and pharmacodynamic parameters

2020 ◽  
Author(s):  
Aldenora Maria Ximenes Rodrigues ◽  
Rayla Kelly Magalhães Costa ◽  
Ranyelison Silva Machado ◽  
Stanley Juan Chavez Gutierrez ◽  
Francisco das Chagas Alves Lima ◽  
...  
Keyword(s):  
In Silico ◽  
Computational Prediction ◽  
Drug Candidate ◽  
Pharmacokinetic Parameters ◽  
Synthetic Analog ◽  
In Silico Studies ◽  
Future Drug ◽  
On Line

AbstractThe process involved in the research, discovery and development of drugs is characterized by high extensive and complex cost linked to scientific and technological innovations, and it is necessary to study and verify the progress of research carried out in the field that results in patent applications. Aniba riparia (Nees) Mez is a plant species often used for therapeutic purposes, where its pharmacological properties are associated to the presence of alkaloids called riparins. 5 synthetic analog compounds (riparins A, B, C, D, E and F) were developed from natural riparins. These molecules, natural and synthetic, showed several pharmacological activities in tests performed in vitro and in vivo, highlighting the Central Nervous System (CNS). The objective of this work was to evaluate the physical-chemical, pharmacokinetic parameters (absorption, distribution, metabolism, excretion and toxicity) and pharmacodynamic parameters (bioactivity and adverse reactions) of Riparin B by means of in silico computational prediction. Online software such as Pre-ADMET, SwissADME, Molinspiration and PASS on line were used for the analysis. Riparin B fits the characteristics of druglikeness, pharmacokinetic properties appropriate to the predicted patterns and activities within the scope for the treatment of AD, demonstrating a possible potential in the inhibition of AChE. Therefore, in silico results allow us to conclude that riparin B is predicted to be a potential future drug candidate, especially via oral administration, due to its relevant Drug-likeness profile, bioavailability, excellent liposolubility and adequate pharmacokinetics, including at the level of CNS, penetrating the blood-brain barrier.

scholarly journals In Vitro, In Vivo, and In Silico Studies of Cumanin Diacetate as a Potential Drug against Trypanosoma cruzi Infection

ACS Omega ◽  
2021 ◽  
Author(s):  
Andrés Sánchez Alberti ◽  
María F. Beer ◽  
Natacha Cerny ◽  
Augusto E. Bivona ◽  
Lucas Fabian ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
In Silico ◽  
Potential Drug ◽  
In Silico Studies ◽  
Cruzi Infection

Recent In Vitro and In Silico Advances in the Understanding of Intranasal Drug Delivery

2020 ◽  
Vol 26 ◽  
Author(s):  
John Chen ◽  
Andrew Martin ◽  
Warren H. Finlay
Keyword(s):  
Drug Delivery ◽  
In Silico ◽  
Local Drug Delivery ◽  
In Vivo Studies ◽  
Intranasal Drug Delivery ◽  
Nasal Sprays ◽  
In Silico Studies ◽  
Drug Delivery Devices

Background: Many drugs are delivered intranasally for local or systemic effect, typically in the form of droplets or aerosols. Because of the high cost of in vivo studies, drug developers and researchers often turn to in vitro or in silico testing when first evaluating the behavior and properties of intranasal drug delivery devices and formulations. Recent advances in manufacturing and computer technologies have allowed for increasingly realistic and sophisticated in vitro and in silico reconstructions of the human nasal airways. Objective: To perform a summary of advances in understanding of intranasal drug delivery based on recent in vitro and in silico studies. Conclusion: The turbinates are a common target for local drug delivery applications, and while nasal sprays are able to reach this region, there is currently no broad consensus across the in vitro and in silico literature concerning optimal parameters for device design, formulation properties and patient technique which would maximize turbinate deposition. Nebulizers are able to more easily target the turbinates, but come with the disadvantage of significant lung deposition. Targeting of the olfactory region of the nasal cavity has been explored for potential treatment of central nervous system conditions. Conventional intranasal devices, such as nasal sprays and nebulizers, deliver very little dose to the olfactory region. Recent progress in our understanding of intranasal delivery will be useful in the development of the next generation of intranasal drug delivery devices.

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