Combined Ligand and Fragment-based Drug Design of Selective Histone Deacetylase-6 Inhibitors
Само за регистроване кориснике
2019
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Histone deacetylase 6 (HDAC6) is unique hydrolase within HDAC family, having pleiotropic deacetylase activity against alpha-tubulin, cortactin and dynein. Comprehensively, HDAC6 controls cell motility, apoptosis and protein folding, whereas alterations in its structure and function are related to the pathogenesis of cancer, neurodegeneration and inflammation. To define structural motifs which guide HDAC6 selectivity, we developed and compared three-dimensional Quantitative Structure-Activity Relationship (3D-QSAR) models for HDAC1 and HDAC6 inhibitors. The reduction of the bias in conformer generation was supported by virtual docking study by using crystal structures of human HDAC1 and HDAC6 isoforms. Following these findings, the combined ligand-based and fragment-based drug design methodologies were used in the design of selective HDAC6 inhibitors. Group of the most promising novel ligands was selected based on the predicted HDAC6 selectivity, pharmacokinetic profile, synthetic tract...ability, and in silico cytotoxicity against the wide range of human cancer cell lines.
Кључне речи:
Rational drug design / 3D-QSAR / Epidrugs / HDAC6Извор:
Molecular Informatics, 2019, 38, 5Издавач:
- Wiley-VCH Verlag GMBH, Weinheim
Финансирање / пројекти:
- Синтеза, квантитативни однос између структуре и дејства, физичко-хемијска карактеризација и анализа фармаколошки активних супстанци (RS-MESTD-Basic Research (BR or ON)-172033)
DOI: 10.1002/minf.201800083
ISSN: 1868-1743
PubMed: 30632697
WoS: 000466504900001
Scopus: 2-s2.0-85059916833
Институција/група
PharmacyTY - JOUR AU - Ružić, Dušan AU - Petković, Miloš AU - Agbaba, Danica AU - Ganesan, A. AU - Nikolić, Katarina PY - 2019 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3369 AB - Histone deacetylase 6 (HDAC6) is unique hydrolase within HDAC family, having pleiotropic deacetylase activity against alpha-tubulin, cortactin and dynein. Comprehensively, HDAC6 controls cell motility, apoptosis and protein folding, whereas alterations in its structure and function are related to the pathogenesis of cancer, neurodegeneration and inflammation. To define structural motifs which guide HDAC6 selectivity, we developed and compared three-dimensional Quantitative Structure-Activity Relationship (3D-QSAR) models for HDAC1 and HDAC6 inhibitors. The reduction of the bias in conformer generation was supported by virtual docking study by using crystal structures of human HDAC1 and HDAC6 isoforms. Following these findings, the combined ligand-based and fragment-based drug design methodologies were used in the design of selective HDAC6 inhibitors. Group of the most promising novel ligands was selected based on the predicted HDAC6 selectivity, pharmacokinetic profile, synthetic tractability, and in silico cytotoxicity against the wide range of human cancer cell lines. PB - Wiley-VCH Verlag GMBH, Weinheim T2 - Molecular Informatics T1 - Combined Ligand and Fragment-based Drug Design of Selective Histone Deacetylase-6 Inhibitors VL - 38 IS - 5 DO - 10.1002/minf.201800083 ER -
@article{ author = "Ružić, Dušan and Petković, Miloš and Agbaba, Danica and Ganesan, A. and Nikolić, Katarina", year = "2019", abstract = "Histone deacetylase 6 (HDAC6) is unique hydrolase within HDAC family, having pleiotropic deacetylase activity against alpha-tubulin, cortactin and dynein. Comprehensively, HDAC6 controls cell motility, apoptosis and protein folding, whereas alterations in its structure and function are related to the pathogenesis of cancer, neurodegeneration and inflammation. To define structural motifs which guide HDAC6 selectivity, we developed and compared three-dimensional Quantitative Structure-Activity Relationship (3D-QSAR) models for HDAC1 and HDAC6 inhibitors. The reduction of the bias in conformer generation was supported by virtual docking study by using crystal structures of human HDAC1 and HDAC6 isoforms. Following these findings, the combined ligand-based and fragment-based drug design methodologies were used in the design of selective HDAC6 inhibitors. Group of the most promising novel ligands was selected based on the predicted HDAC6 selectivity, pharmacokinetic profile, synthetic tractability, and in silico cytotoxicity against the wide range of human cancer cell lines.", publisher = "Wiley-VCH Verlag GMBH, Weinheim", journal = "Molecular Informatics", title = "Combined Ligand and Fragment-based Drug Design of Selective Histone Deacetylase-6 Inhibitors", volume = "38", number = "5", doi = "10.1002/minf.201800083" }
Ružić, D., Petković, M., Agbaba, D., Ganesan, A.,& Nikolić, K.. (2019). Combined Ligand and Fragment-based Drug Design of Selective Histone Deacetylase-6 Inhibitors. in Molecular Informatics Wiley-VCH Verlag GMBH, Weinheim., 38(5). https://doi.org/10.1002/minf.201800083
Ružić D, Petković M, Agbaba D, Ganesan A, Nikolić K. Combined Ligand and Fragment-based Drug Design of Selective Histone Deacetylase-6 Inhibitors. in Molecular Informatics. 2019;38(5). doi:10.1002/minf.201800083 .
Ružić, Dušan, Petković, Miloš, Agbaba, Danica, Ganesan, A., Nikolić, Katarina, "Combined Ligand and Fragment-based Drug Design of Selective Histone Deacetylase-6 Inhibitors" in Molecular Informatics, 38, no. 5 (2019), https://doi.org/10.1002/minf.201800083 . .