scholarly journals In silico model and design of novel 5α-reductase inhibitors for treatment of benign prostatic hyperplasia

2021 ◽  
Vol 18 (10) ◽  
pp. 2081-2088
Author(s):  
Qi Lin ◽  
Danhua Lin ◽  
Ying Zhang
Keyword(s):  
In Silico ◽  
Docking Simulation ◽  
Prostate Hyperplasia ◽  
Online Programs ◽  
Lead Compounds ◽  
Reductase Inhibitors ◽  
Potent Inhibition ◽  
Simulation Based ◽  
Pharmacokinetic Properties ◽  
In Silico Molecular Docking

Purpose: To carry out in silico design of 5α-reductase inhibitors and study their potential for use in the treatment of benign prostate hyperplasia (BPH). Methods: In silico molecular docking simulation-based virtual screening of NCI Diversity Set-II containing 1880 diverse ligands was performed against human 5α-reductase for identification of potential lead molecules. The pharmacological properties and toxicity of the lead compounds were determined using software, Marvin Sketch and OSIRIS online programs, respectively. Results: Three compounds: ZINC13099050, ZINC01569237 and ZINC17995347_2 showed potent inhibition of 5α-reductase enzyme protein and good pharmacokinetic properties without any serious toxic effects. Conclusion: The selected lead molecules are promising inhibitors of 5α-reductase. They are recommended for further structure-based development of drugs for the treatment of BPH.

scholarly journals In-silico design of novel myocilin inhibitors for glaucoma therapy

2017 ◽  
Vol 16 (10) ◽  
pp. 2527-2533
Author(s):  
Min Tang ◽  
Yang Fu ◽  
Ying Fan ◽  
Ming-Shui Fu ◽  
Zhi Zheng ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
In Silico ◽  
Binding Energies ◽  
Computational Approaches ◽  
Screening Technique ◽  
Lead Compounds ◽  
Potent Inhibition ◽  
Pharmacokinetic Properties ◽  
Molecular Libraries

Purpose: To explore newer computational approaches in the design of novel myocilin inhibitors for the treatment of glaucoma.Methods: An in-silico virtual screening technique based on simulation of molecular docking was utilised to design a novel myocilin inhibitors for the treatment of  glaucoma. The designed novel molecules were theoretically evaluated to predict their pharmacokinetic properties and toxic effects. Lead molecules were screened out in virtual screening technique on the basis of low binding energies obtained in AutoDock based molecular docking simulation.Results: Out of ten top lead compounds screened, ZINC01729523 and ZINC04692015 were promising, having shown potent inhibition of myocilin, good pharmacokinetic properties and absence of any toxic effects.Conclusion: In-silico virtual screening of molecular libraries containing a large number of ligands is very useful for short-listing of potential lead molecules for further structure-based discovery of antiglaucoma-drugs.Keywords: Glaucoma, Myocilin, Docking, Virtual-screening, Autodock, Ligand, Drug design

scholarly journals In silico ADME in drug design – enhancing the impact

ADMET & DMPK ◽  
2018 ◽  
Vol 6 (1) ◽  
pp. 15 ◽  
Author(s):  
Susanne Winiwarter ◽  
Ernst Ahlberg ◽  
Edmund Watson ◽  
Ioana Oprisiu ◽  
Mickael Mogemark ◽  
...  
Keyword(s):  
In Silico ◽  
In Vitro Assays ◽  
Lead Compounds ◽  
Human Dose ◽  
Pharmacokinetic Properties ◽  
In Silico Predictions ◽  
In Silico Models ◽  
The Impact ◽  
Selection Of

<p>Each year the pharmaceutical industry makes thousands of compounds, many of which do not meet the desired efficacy or pharmacokinetic properties, describing the absorption, distribution, metabolism and excretion (ADME) behavior. Parameters such as lipophilicity, solubility and metabolic stability can be measured in high throughput in vitro assays. However, a compound needs to be synthesized in order to be tested. In silico models for these endpoints exist, although with varying quality. Such models can be used before synthesis and, together with a potency estimation, influence the decision to make a compound. In practice, it appears that often only one or two predicted properties are considered prior to synthesis, usually including a prediction of lipophilicity. While it is important to use all information when deciding which compound to make, it is somewhat challenging to combine multiple predictions unambiguously. This work investigates the possibility of combining in silico ADME predictions to define the minimum required potency for a specified human dose with sufficient confidence. Using a set of drug discovery compounds,in silico predictions were utilized to compare the relative ranking based on minimum potency calculation with the outcomes from the selection of lead compounds. The approach was also tested on a set of marketed drugs and the influence of the input parameters investigated.</p>

scholarly journals In Silico Screening of Sesquiterpene Lactones as Aldose Reductase Inhibitors

2021 ◽  
Vol 28 (2) ◽  
pp. 64-69
Author(s):  
A.M. Alhassan ◽  
I. Malami
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Aldose Reductase ◽  
In Silico ◽  
Sesquiterpene Lactones ◽  
Docking Simulation ◽  
Binding Energies ◽  
In Silico Docking ◽  
Aldose Reductase Inhibitors ◽  
Reductase Inhibitors

Aldose reductase, a key enzyme of the polyol pathway catalyses NADPH-dependent reduction of glucose to sorbitol. Increased activity of this enzyme is considered a major factor contributing to the development of diabetic complications hence could be an important target in the treatment of these complications. In this work, a database of sesquiterpenes was prepared and screened for their drug-like properties based on the Lipinski’s rule of 5. The co-crystallised structure of aldose reductase was obtained from the Protein Databank and prepared for docking. In silico docking experiments was performed on Autodock tools using 198 sesquiterpene lactones that passed screening, and compounds with the lowest binding energy and favourable binding interactions were selected for molecular docking simulation. Six of the best ranking compounds selected had binding energies ranging from–11.96 Kcal/mol to -9.45 Kcal/mol  and were comparable to the energy of the standard inhibitor Idd594 used in the study. They also show good complementarity in their binding to the residues of the binding pocket. The results suggest that dehydrooopodin (1), 11(S),13-dihydrolactucopicrin (2), and Chrysanin (3) offered potential inhibitory activities toward aldose reductase and may serve as lead compounds for in vivo validation as aldose reductase inhibitors. Keywords: Sesquiterpene lactones, Aldose reductase, Binding energy, Molecular docking, Autodock

scholarly journals In silico Molecular Docking of Anthraquinone Identified from Boerhavia diffusa Linn against Bax and Bcl-2 Gene

2021 ◽  
pp. 352-359
Author(s):  
U. Kanagavalli ◽  
E. Deboral ◽  
M. D. Lakshmipriya ◽  
A. Mohamed Sadiq ◽  
A. Mohana Priya
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Traditional Approach ◽  
Docking Simulation ◽  
Data Bank ◽  
Substantial Contribution ◽  
Computational Technique ◽  
Medical Environment ◽  
Multiple Protein ◽  
In Silico Molecular Docking

In today's medical environment, natural products have made a substantial contribution to the therapeutic approach in the treatment of diseases ranging from the simple to the complex. The old or traditional approach of standardization in medicinal plant research is a time-consuming, costly, and to some extent antiquated process. As a result, a computational technique that includes an in silico molecular docking simulation study has become an important tool for drug development, standardisation, and screening of phytochemicals. To investigate the cardioprotective research and the interaction of the strong chemical against Bax and Bcl-2 cardiomyocyte gene, docking was conducted using multiple Protein Data Bank files (3EOO, 3D2U, 2I42, and 3D2Y). The Anthraquinone has shown more potent interaction with apoptotic regulators Bcl-2 and Bax genes by showing good binding energy. The study also evident that Anthraquinone (UBA) was an ideal drug agent with better drug likeliness.  Further, the compound can be used as therapeutic molecule for myocardial infarction. However, the results are preliminary and experimental evaluation will be carried out in near future.

The Antiviral and Antimalarial Drug Repurposing in Quest of Chemotherapeutics to Combat COVID-19 Utilizing Structure-Based Molecular Docking

2020 ◽  
Vol 23 ◽  
Author(s):  
Sisir Nandi ◽  
Mohit Kumar ◽  
Mridula Saxena ◽  
Anil Kumar Saxena
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Drug Repurposing ◽  
Clinical Settings ◽  
The Novel ◽  
In Silico Docking ◽  
Biochemical Mechanisms ◽  
Novel Coronavirus ◽  
In Silico Molecular Docking

Background: The novel coronavirus disease (COVID-19) is caused by a new strain (SARS-CoV-2) erupted in 2019. Nowadays, it is a great threat that claims uncountable lives worldwide. There is no specific chemotherapeutics developed yet to combat COVID-19. Therefore, scientists have been devoted in the quest of the medicine that can cure COVID- 19. Objective: Existing antivirals such as ASC09/ritonavir, lopinavir/ritonavir with or without umifenovir in combination with antimalarial chloroquine or hydroxychloroquine have been repurposed to fight the current coronavirus epidemic. But exact biochemical mechanisms of these drugs towards COVID-19 have not been discovered to date. Method: In-silico molecular docking can predict the mode of binding to sort out the existing chemotherapeutics having a potential affinity towards inhibition of the COVID-19 target. An attempt has been made in the present work to carry out docking analyses of 34 drugs including antivirals and antimalarials to explain explicitly the mode of interactions of these ligands towards the COVID-19protease target. Results: 13 compounds having good binding affinity have been predicted towards protease binding inhibition of COVID-19. Conclusion: Our in silico docking results have been confirmed by current reports from clinical settings through the citation of suitable experimental in vitro data available in the published literature.

Sign in / Sign up

Export Citation Format

Share Document