Drug Repositioning: Principles, Resources, and Application of Structure-Based Virtual Screening for the Identification of Anticancer Agents

Author(s):  
Imlimaong Aier ◽  
Pritish Kumar Varadwaj
2016 ◽  
Vol 19 (9) ◽  
pp. 735-751 ◽  
Author(s):  
Preeti Patel ◽  
Avineesh Singh ◽  
Vijay Patel ◽  
Deepak Jain ◽  
Ravichandran Veerasamy ◽  
...  

Antibiotics ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 92 ◽  
Author(s):  
Alessia Catalano ◽  
Domenico Iacopetta ◽  
Michele Pellegrino ◽  
Stefano Aquaro ◽  
Carlo Franchini ◽  
...  

Antimicrobials have allowed medical advancements over several decades. However, the continuous emergence of antimicrobial resistance restricts efficacy in treating infectious diseases. In this context, the drug repositioning of already known biological active compounds to antimicrobials could represent a useful strategy. In 2002 and 2003, the SARS-CoV pandemic immobilized the Far East regions. However, the drug discovery attempts to study the virus have stopped after the crisis declined. Today’s COVID-19 pandemic could probably have been avoided if those efforts against SARS-CoV had continued. Recently, a new coronavirus variant was identified in the UK. Because of this, the search for safe and potent antimicrobials and antivirals is urgent. Apart from antiviral treatment for severe cases of COVID-19, many patients with mild disease without pneumonia or moderate disease with pneumonia have received different classes of antibiotics. Diarylureas are tyrosine kinase inhibitors well known in the art as anticancer agents, which might be useful tools for a reposition as antimicrobials. The first to come onto the market as anticancer was sorafenib, followed by some other active molecules. For this interesting class of organic compounds antimicrobial, antiviral, antithrombotic, antimalarial, and anti-inflammatory properties have been reported in the literature. These numerous properties make these compounds interesting for a new possible pandemic considering that, as well as for other viral infections also for CoVID-19, a multitarget therapeutic strategy could be favorable. This review is meant to be an overview on diarylureas, focusing on their biological activities, not dwelling on the already known antitumor activity. Quite a lot of papers present in the literature underline and highlight the importance of these molecules as versatile scaffolds for the development of new and promising antimicrobials and multitarget agents against new pandemic events.


2015 ◽  
Vol 16 (2) ◽  
pp. 3202-3212 ◽  
Author(s):  
Chih-Hung Chuang ◽  
Ta-Chun Cheng ◽  
Yu-Ling Leu ◽  
Kuo-Hsiang Chuang ◽  
Shey-Cherng Tzou ◽  
...  

2022 ◽  
Vol 1249 ◽  
pp. 131648
Author(s):  
Dorota Stary ◽  
Jędrzej Kukułowicz ◽  
Izabella Góral ◽  
Hanna Baltrukevich ◽  
Marharyta Barbasevich ◽  
...  

2020 ◽  
Vol 11 (5) ◽  
pp. 832-838 ◽  
Author(s):  
Fabrizio Manetti ◽  
Barbara Stecca ◽  
Roberta Santini ◽  
Luisa Maresca ◽  
Giuseppe Giannini ◽  
...  

Author(s):  
Natesh Singh ◽  
Ludovic Chaput ◽  
Bruno O Villoutreix

Abstract The interplay between life sciences and advancing technology drives a continuous cycle of chemical data growth; these data are most often stored in open or partially open databases. In parallel, many different types of algorithms are being developed to manipulate these chemical objects and associated bioactivity data. Virtual screening methods are among the most popular computational approaches in pharmaceutical research. Today, user-friendly web-based tools are available to help scientists perform virtual screening experiments. This article provides an overview of internet resources enabling and supporting chemical biology and early drug discovery with a main emphasis on web servers dedicated to virtual ligand screening and small-molecule docking. This survey first introduces some key concepts and then presents recent and easily accessible virtual screening and related target-fishing tools as well as briefly discusses case studies enabled by some of these web services. Notwithstanding further improvements, already available web-based tools not only contribute to the design of bioactive molecules and assist drug repositioning but also help to generate new ideas and explore different hypotheses in a timely fashion while contributing to teaching in the field of drug development.


Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3909 ◽  
Author(s):  
Amit Kumar Halder ◽  
Amal Kanta Giri ◽  
Maria Natália Dias Soeiro Cordeiro

Two isoforms of extracellular regulated kinase (ERK), namely ERK-1 and ERK-2, are associated with several cellular processes, the aberration of which leads to cancer. The ERK-1/2 inhibitors are thus considered as potential agents for cancer therapy. Multitarget quantitative structure–activity relationship (mt-QSAR) models based on the Box–Jenkins approach were developed with a dataset containing 6400 ERK inhibitors assayed under different experimental conditions. The first mt-QSAR linear model was built with linear discriminant analysis (LDA) and provided information regarding the structural requirements for better activity. This linear model was also utilised for a fragment analysis to estimate the contributions of ring fragments towards ERK inhibition. Then, the random forest (RF) technique was employed to produce highly predictive non-linear mt-QSAR models, which were used for screening the Asinex kinase library and identify the most potential virtual hits. The fragment analysis results justified the selection of the hits retrieved through such virtual screening. The latter were subsequently subjected to molecular docking and molecular dynamics simulations to understand their possible interactions with ERK enzymes. The present work, which utilises in-silico techniques such as multitarget chemometric modelling, fragment analysis, virtual screening, molecular docking and dynamics, may provide important guidelines to facilitate the discovery of novel ERK inhibitors.


2021 ◽  
Vol 9 (4) ◽  
pp. 481-491
Author(s):  
Megana KSNM ◽  
◽  
Suneetha Y ◽  

Present days increasing concern about the identification of potential non-toxic drug candidates against several cancers is very important. The current study was carried out to discover the novel phytochemicals as effective anticancer agents against the selected protein (i.e., EGFR), which is a promising target for moderating triple-negative breast cancer (TNBC). Various studies showed that the natural constituents have a strong anti-tumor capacity and inhibiting tumor growth. Here structure-based virtual screening and molecular docking studies have been recognized as rational tactics for the recognition of novel drug candidates against the binding domain of EGFR (PDB code: 3GKW & 5FEE). Furthermore, the drug-likeness, adverse effects, and toxicogenomics effects were assessed with the help of various computational tools. Virtual screening was reported that 4 drug candidates i.e., CID: 65064; CID: 5280443; CID: 440735, and CID: 5280343 showed reliable consequences with fewer side effects and more efficient for the selected proteins. The overall effects indicated that renowned hits could be developed as reference skeletons for novel inhibitors envisaging EGFR to ameliorate TNBC.


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