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
Citations
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Journal ArticleDOI
Small molecule HDAC inhibitors: Promising agents for breast cancer treatment.
TL;DR: In conclusion, HDACs have shown desirable effects on breast cancer, especially when they are used in combination with other anticancer agents, and more multicenter and randomized Phase III studies are expected to be conducted pushing promising new therapies closer to the market.
Journal ArticleDOI
Quinazoline-Based Hydroxamic Acids: Design, Synthesis, and Evaluation of Histone Deacetylase Inhibitory Effects and Cytotoxicity
Doan Thanh Hieu,Duong Tien Anh,Pham-The Hai,Le-Thi-Thu Huong,Eun Jae Park,Jeong Eun Choi,Jong Soon Kang,Phan Thi Phuong Dung,Sang-Bae Han,Nguyen Hai Nam +9 more
TL;DR: Detailed investigation on the estimation of absorption, distribution, metabolism, excretion, and toxicity (ADMET) suggested that compounds 4g, 6c, and 6g, while showing potent HDAC2 inhibitory activity and cytotoxicity, also potentially displayed ADMET characteristics desirable to be expected as promising anticancer drug candidates.
Journal ArticleDOI
Evaluation of pyrrole-2,3-dicarboxylate derivatives: Synthesis, DFT analysis, molecular docking, virtual screening and in vitro anti-hepatic cancer study
Iqbal Azad,Asif Jafri,Tahmeena Khan,Yusuf Akhter,Arshad,Firoj Hassan,Naseem Ahmad,Abdul Rahman Khan,Malik Nasibullah +8 more
TL;DR: Pyrrole-2,3-dicarboxylate derivatives synthesized in this study significantly inhibited the growth of HepG2 cells in a dose-dependent manner and may be proven to be novel therapeutic candidates to cure cancer.
Journal ArticleDOI
Conformal prediction of HDAC inhibitors.
Ulf Norinder,Ulf Norinder,J. Jesús Naveja,J. Jesús Naveja,Edgar López-López,Daniel Mucs,José L. Medina-Franco +6 more
TL;DR: This work introduces a novel approach for epigenetic quantitative structure–activity relationship (QSAR) modelling using conformal prediction and discusses the development of models for 11 sets of inhibitors of histone deacetylases, which are one of the major epigenetic target families that have been screened.
References
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Journal ArticleDOI
A rational workflow for sequential virtual screening of chemical libraries on searching for new tyrosinase inhibitors.
Huong Le-Thi-Thu,Gerardo M. Casañola-Martin,Yovani Marrero-Ponce,Antonio Rescigno,Concepción Abad,Mahmud Tareq Hassan Khan +5 more
TL;DR: This chapter is focused in the different components of a predictive modeling workflow for the identification and prioritization of potential new compounds with activity against the tyrosinase enzyme, trying to combine different virtual screening data mining techniques in a sequential manner to avoid the usually expensive and time consuming traditional methods.
Journal ArticleDOI
3-D QSAR Studies on Histone Deacetylase Inhibitors. A GOLPE/GRID Approach on Different Series of Compounds.
TL;DR: In this paper, three-dimensional quantitative structure-activity relationships (3D-QSARs) analyses were conducted on four series of HDAC inhibitors using the GRID/GOLPE combination using structure-based alignment.
Book ChapterDOI
Quantitative Structure–Activity Relationship Studies on Hydroxamic Acids Acting as Histone Deacetylase Inhibitors
TL;DR: A brief review of the QSAR and molecular modeling studies performed on hydroxamic acid derivatives acting as histone deacetylase inhibitors that have been studied as anticancer agents shows that the anticancer activity of these compounds is basically controlled by their hydrophobic and steric properties.
Journal ArticleDOI
Quantitative Structure-Activity Relationship Study of Amino Acid Derivatives as Histone Deacetylase Inhibitors using the Genetic Algorithm – Multiple Linear Regression
TL;DR: In this article, the quantitative structure-activity relationship (QSAR) of the amino acid derivatives for prediction of histone deacetylase inhibitors activity was studied, and the GA-MLR model with six selected descriptors was obtained.