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Exploring different classification-dependent QSAR modelling strategies for HDAC3 inhibitors in search of meaningful structural contributors.
Jha, T; Jana, R; Banerjee, S; Baidya, S K; Amin, S A; Gayen, S; Ghosh, B; Adhikari, N.
Afiliación
  • Jha T; Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
  • Jana R; Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
  • Banerjee S; Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
  • Baidya SK; Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
  • Amin SA; Laboratory of Drug Design and Discovery, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
  • Gayen S; Laboratory of Drug Design and Discovery, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
  • Ghosh B; Epigenetic Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science-Pilani, Hyderabad, India.
  • Adhikari N; Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
SAR QSAR Environ Res ; 35(5): 367-389, 2024 May.
Article en En | MEDLINE | ID: mdl-38757181
ABSTRACT
Histone deacetylase 3 (HDAC3), a Zn2+-dependent class I HDACs, contributes to numerous disorders such as neurodegenerative disorders, diabetes, cardiovascular disease, kidney disease and several types of cancers. Therefore, the development of novel and selective HDAC3 inhibitors might be promising to combat such diseases. Here, different classification-based molecular modelling studies such as Bayesian classification, recursive partitioning (RP), SARpy and linear discriminant analysis (LDA) were conducted on a set of HDAC3 inhibitors to pinpoint essential structural requirements contributing to HDAC3 inhibition followed by molecular docking study and molecular dynamics (MD) simulation analyses. The current study revealed the importance of hydroxamate function for Zn2+ chelation as well as hydrogen bonding interaction with Tyr298 residue. The importance of hydroxamate function for higher HDAC3 inhibition was noticed in the case of Bayesian classification, recursive partitioning and SARpy models. Also, the importance of substituted thiazole ring was revealed, whereas the presence of linear alkyl groups with carboxylic acid function, any type of ester function, benzodiazepine moiety and methoxy group in the molecular structure can be detrimental to HDAC3 inhibition. Therefore, this study can aid in the design and discovery of effective novel HDAC3 inhibitors in the future.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Teorema de Bayes / Relación Estructura-Actividad Cuantitativa / Inhibidores de Histona Desacetilasas / Simulación de Dinámica Molecular / Simulación del Acoplamiento Molecular / Histona Desacetilasas Idioma: En Revista: SAR QSAR Environ Res Asunto de la revista: SAUDE AMBIENTAL Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Teorema de Bayes / Relación Estructura-Actividad Cuantitativa / Inhibidores de Histona Desacetilasas / Simulación de Dinámica Molecular / Simulación del Acoplamiento Molecular / Histona Desacetilasas Idioma: En Revista: SAR QSAR Environ Res Asunto de la revista: SAUDE AMBIENTAL Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Reino Unido