In Silico HCT116 Human Colon Cancer Cell-Based Models En Route to the Discovery of Lead-Like Anticancer Drugs

Biomolecules
Sara CruzFlorbela Pereira

Abstract

To discover new inhibitors against the human colon carcinoma HCT116 cell line, two quantitative structure⁻activity relationship (QSAR) studies using molecular and nuclear magnetic resonance (NMR) descriptors were developed through exploration of machine learning techniques and using the value of half maximal inhibitory concentration (IC50). In the first approach, A, regression models were developed using a total of 7339 molecules that were extracted from the ChEMBL and ZINC databases and recent literature. The performance of the regression models was successfully evaluated by internal and external validations, the best model achieved R² of 0.75 and 0.73 and root mean square error (RMSE) of 0.66 and 0.69 for the training and test sets, respectively. With the inherent time-consuming efforts of working with natural products (NPs), we conceived a new NP drug hit discovery strategy that consists in frontloading samples with 1D NMR descriptors to predict compounds with anticancer activity prior to bioactivity screening for NPs discovery, approach B. The NMR QSAR classification models were built using 1D NMR data (¹H and 13C) as descriptors, from 50 crude extracts, 55 fractions and five pure compounds obtained from actinobacteria isol...Continue Reading

References

Nov 25, 2003·Journal of Chemical Information and Computer Sciences·Vladimir SvetnikBradley P Feuston
Jul 28, 2005·Journal of Chemical Information and Modeling·Shengqiao LiSidney C Soderholm
Apr 5, 2007·Journal of Chemical Information and Modeling·Debojyoti DuttaTing Chen
Feb 1, 2008·Journal of Medicinal Chemistry·M Paul Gleeson
Jun 8, 2010·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Paola GramaticaDomenico Osella
Nov 26, 2010·British Journal of Pharmacology·J P HughesK L Philpott
Mar 23, 2011·Journal of Computational Chemistry·Chun Wei Yap
Sep 13, 2011·Bioorganic & Medicinal Chemistry Letters·Soon Young ShinYoongho Lim
Dec 30, 2011·Journal of Natural Products·David CampRonald J Quinn
Mar 30, 2012·Bioorganic & Medicinal Chemistry Letters·Jiye HyunYoongho Lim
Jul 1, 2006·Expert Opinion on Drug Discovery·David E Clark
Jan 2, 2014·Pharmacological Reviews·Gregory SliwoskiEdward W Lowe
Dec 17, 2014·Organic & Biomolecular Chemistry·Adel S GirgisAlan R Katritzky
Feb 20, 2015·Expert Opinion on Drug Discovery·Chanin Nantasenamat, Virapong Prachayasittikul
Mar 20, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Florbela PereiraSusana P Gaudêncio
Apr 4, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jarosław SławińskiTomasz Bączek
Apr 9, 2015·Natural Product Reports·Susana P Gaudêncio, Florbela Pereira
Oct 20, 2015·Journal of Chemical Information and Modeling·Teague Sterling, John J Irwin
Oct 28, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Beata ŻołnowskaKrzysztof Szafrański
Nov 29, 2015·Nucleic Acids Research·Dennis KlementzStefan Günther
Feb 2, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Johann Gasteiger
Mar 2, 2016·Journal of Health Economics·Joseph A DiMasiRonald W Hansen
Jun 14, 2016·Computational and Structural Biotechnology Journal·Theodora KatsilaMinos-Timotheos Matsoukas
Dec 3, 2016·Nucleic Acids Research·Anna GaultonAndrew R Leach

❮ Previous
Next ❯

Methods Mentioned

BETA
nuclear magnetic resonance
NMR

Software Mentioned

ChEMBL
SMILES
MDEO
RandomForest
CoMFA
GraphPad Prism
XLogP
ACD Processor
JChem
CoMSIA

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.