Journal ArticleDOI
Quantitative structure–activity relationship analysis and virtual screening studies for identifying HDAC2 inhibitors from known HDAC bioactive chemical libraries
Hai Pham-The,Gerardo M. Casañola-Martin,Karel Diéguez-Santana,Nam Nguyen-Hai,N T Ngoc,L Vu-Duc,Huong Le-Thi-Thu +6 more
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TLDR
This study illustrates the power of ML-based QSAR approaches for the screening and discovery of potent, isoform-selective HDACIs.Abstract:
Histone deacetylases (HDAC) are emerging as promising targets in cancer, neuronal diseases and immune disorders. Computational modelling approaches have been widely applied for the virtual screening and rational design of novel HDAC inhibitors. In this study, different machine learning (ML) techniques were applied for the development of models that accurately discriminate HDAC2 inhibitors form non-inhibitors. The obtained models showed encouraging results, with the global accuracy in the external set ranging from 0.83 to 0.90. Various aspects related to the comparison of modelling techniques, applicability domain and descriptor interpretations were discussed. Finally, consensus predictions of these models were used for screening HDAC2 inhibitors from four chemical libraries whose bioactivities against HDAC1, HDAC3, HDAC6 and HDAC8 have been known. According to the results of virtual screening assays, structures of some hits with pair-isoform-selective activity (between HDAC2 and other HDACs) were revealed. This study illustrates the power of ML-based QSAR approaches for the screening and discovery of potent, isoform-selective HDACIs.read more
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Journal ArticleDOI
Exploration of certain 1,3-oxazole- and 1,3-thiazole-based hydroxamic acids as histone deacetylase inhibitors and antitumor agents
Duong Tien Anh,Pham-The Hai,Le-Thi-Thu Huong,Eun Jae Park,Hye Won Jun,Jong Soon Kang,Joo-Hee Kwon,Do Thi Mai Dung,Vu Tran Anh,Van Thi My Hue,Sang-Bae Han,Nguyen Hai Nam +11 more
TL;DR: This study demonstrates that simple 1, 3-oxazole- and 1,3-thiazole-based hydroxamic acids are also promising as antitumor agents and HDAC inhibitors and these results should provide valuable information for further design of more potent HDAC inhibitor and antitumour agents.
Journal ArticleDOI
Integrating structure and ligand-based approaches for modelling the histone deacetylase inhibition activity of hydroxamic acid derivatives
Hai Pham-The,Huong Le-Thi-Thu +1 more
TL;DR: In this article, structure and ligand-based drug design approaches have been integrated to accurately predict the inhibition activity of hydroxamic acid (HA) derivatives against the histone deacetylase-2 enzyme (HDAC2) by docking assays.
Journal ArticleDOI
Beyond model interpretability using LDA and decision trees for α-amylase and α-glucosidase inhibitor classification studies.
Karel Diéguez-Santana,Oscar Miguel Rivera-Borroto,Amilkar Puris,Hai Pham-The,Huong Le-Thi-Thu,Bakhtiyor Rasulev,Gerardo M. Casañola-Martin +6 more
TL;DR: The present results provided a double‐target approach for increasing the estimation of antidiabetic chemicals identification aimed by double‐way workflow in virtual screening pipelines.
Journal ArticleDOI
Novel 4-Oxoquinazoline-Based N-Hydroxypropenamides as Histone Deacetylase Inhibitors: Design, Synthesis, and Biological Evaluation.
Duong Tien Anh,Pham-The Hai,Le D Huy,Hoang B Ngoc,Trinh T M Ngoc,Do Thi Mai Dung,Eun Jae Park,In K Song,Jong Soon Kang,Joo-Hee Kwon,Truong Thanh Tung,Sang-Bae Han,Nguyen Hai Nam +12 more
TL;DR: In this article, a series of novel 4-oxoquinazoline-based N-hydroxypropenamides (9a-m and 10a -m) were designed, synthesized, and evaluated for their inhibitory and cytotoxicity activities against histone deacetylase (HDAC) against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23, NCI23, lung cancer) and revealed some important features contributing to the inhibitory activity of synthesized compounds.
Journal ArticleDOI
Applying comparative molecular modelling techniques on diverse hydroxamate-based HDAC2 inhibitors: an attempt to identify promising structural features for potent HDAC2 inhibition
TL;DR: The implementation of a combined comparative 2D and 3D molecular modelling techniques was done on a group of 92 diverse hydroxamate derivatives having a wide range of HDAC2 inhibitory potency, upholding the importance of groups like triazole and benzyl moieties along with the molecular fields that are crucial for regulatingHDAC2 inhibition.
References
More filters
Journal ArticleDOI
The meaning and use of the area under a receiver operating characteristic (ROC) curve.
TL;DR: A representation and interpretation of the area under a receiver operating characteristic (ROC) curve obtained by the "rating" method, or by mathematical predictions based on patient characteristics, is presented and it is shown that in such a setting the area represents the probability that a randomly chosen diseased subject is (correctly) rated or ranked with greater suspicion than a random chosen non-diseased subject.
Book
Data Mining
TL;DR: In this paper, generalized estimating equations (GEE) with computing using PROC GENMOD in SAS and multilevel analysis of clustered binary data using generalized linear mixed-effects models with PROC LOGISTIC are discussed.
Journal ArticleDOI
A caution regarding rules of thumb for variance inflation factors.
TL;DR: In this article, the authors examined the effect of the variance inflation factor (VIF) on the results of regression analyses, and found that threshold values of the VIF need to be evaluated in the context of several other factors that influence the variance of regression coefficients.