Rational drug design of histone deacetylase 6 inhibitors
Апстракт
Activity of the histone deacetylases (HDACs) has an essential influence on histone posttranslational
modifications. Therefore, alterations in the structure and expression of HDACs isoforms are strongly related to
the pathogenesis of inflammation, cancer, and neurodegeneration. The HDACs became extensively examined
targets in novel drug discovery. The HDAC6 isoform is a non-histone cytoplasmic deacetylase, manly involved
in deacetylation of α-tubulin, cortactin, and heat shock protein 90 (Hsp90) [1]. Our rational drug design study
was focused on identification of selective histone deacetylase 6 (HDAC6) inhibitors by use of combined ligand
and structure based methodologies. Based on the 3D-QSAR (Quantitative Structure Activity Relationship)
modeling of HDAC6 inhibitors were defined specific molecular determinants for selective HDAC6 inhibition
and further applied for fragment based design of selective HDAC6 inhibitors. Recently resolved crystal structure
of second human catalyti...c domain of HDAC-6 enzyme (5EDU) [2] was used in virtual docking study of the
examined inhibitors.
Извор:
EFMC-ISMC, XXV EFMC International Symposium on Medicinal Chemistry, Book of Abstract, 2018, 305-305Издавач:
- Section for Medicinal Chemistry of the Slovenian Pharmaceutical Society
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)
Напомена:
- XXV EFMC International Symposium on Medicinal Chemistry, Ljubljana, Slovenia, September 2-6, 2018
Институција/група
PharmacyTY - CONF AU - Ružić, Dušan AU - Nikolić, Katarina AU - Petković, Miloš AU - Ganesan, A. AU - Agbaba, Danica PY - 2018 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4894 AB - Activity of the histone deacetylases (HDACs) has an essential influence on histone posttranslational modifications. Therefore, alterations in the structure and expression of HDACs isoforms are strongly related to the pathogenesis of inflammation, cancer, and neurodegeneration. The HDACs became extensively examined targets in novel drug discovery. The HDAC6 isoform is a non-histone cytoplasmic deacetylase, manly involved in deacetylation of α-tubulin, cortactin, and heat shock protein 90 (Hsp90) [1]. Our rational drug design study was focused on identification of selective histone deacetylase 6 (HDAC6) inhibitors by use of combined ligand and structure based methodologies. Based on the 3D-QSAR (Quantitative Structure Activity Relationship) modeling of HDAC6 inhibitors were defined specific molecular determinants for selective HDAC6 inhibition and further applied for fragment based design of selective HDAC6 inhibitors. Recently resolved crystal structure of second human catalytic domain of HDAC-6 enzyme (5EDU) [2] was used in virtual docking study of the examined inhibitors. PB - Section for Medicinal Chemistry of the Slovenian Pharmaceutical Society C3 - EFMC-ISMC, XXV EFMC International Symposium on Medicinal Chemistry, Book of Abstract T1 - Rational drug design of histone deacetylase 6 inhibitors SP - 305 EP - 305 UR - https://hdl.handle.net/21.15107/rcub_farfar_4894 ER -
@conference{ author = "Ružić, Dušan and Nikolić, Katarina and Petković, Miloš and Ganesan, A. and Agbaba, Danica", year = "2018", abstract = "Activity of the histone deacetylases (HDACs) has an essential influence on histone posttranslational modifications. Therefore, alterations in the structure and expression of HDACs isoforms are strongly related to the pathogenesis of inflammation, cancer, and neurodegeneration. The HDACs became extensively examined targets in novel drug discovery. The HDAC6 isoform is a non-histone cytoplasmic deacetylase, manly involved in deacetylation of α-tubulin, cortactin, and heat shock protein 90 (Hsp90) [1]. Our rational drug design study was focused on identification of selective histone deacetylase 6 (HDAC6) inhibitors by use of combined ligand and structure based methodologies. Based on the 3D-QSAR (Quantitative Structure Activity Relationship) modeling of HDAC6 inhibitors were defined specific molecular determinants for selective HDAC6 inhibition and further applied for fragment based design of selective HDAC6 inhibitors. Recently resolved crystal structure of second human catalytic domain of HDAC-6 enzyme (5EDU) [2] was used in virtual docking study of the examined inhibitors.", publisher = "Section for Medicinal Chemistry of the Slovenian Pharmaceutical Society", journal = "EFMC-ISMC, XXV EFMC International Symposium on Medicinal Chemistry, Book of Abstract", title = "Rational drug design of histone deacetylase 6 inhibitors", pages = "305-305", url = "https://hdl.handle.net/21.15107/rcub_farfar_4894" }
Ružić, D., Nikolić, K., Petković, M., Ganesan, A.,& Agbaba, D.. (2018). Rational drug design of histone deacetylase 6 inhibitors. in EFMC-ISMC, XXV EFMC International Symposium on Medicinal Chemistry, Book of Abstract Section for Medicinal Chemistry of the Slovenian Pharmaceutical Society., 305-305. https://hdl.handle.net/21.15107/rcub_farfar_4894
Ružić D, Nikolić K, Petković M, Ganesan A, Agbaba D. Rational drug design of histone deacetylase 6 inhibitors. in EFMC-ISMC, XXV EFMC International Symposium on Medicinal Chemistry, Book of Abstract. 2018;:305-305. https://hdl.handle.net/21.15107/rcub_farfar_4894 .
Ružić, Dušan, Nikolić, Katarina, Petković, Miloš, Ganesan, A., Agbaba, Danica, "Rational drug design of histone deacetylase 6 inhibitors" in EFMC-ISMC, XXV EFMC International Symposium on Medicinal Chemistry, Book of Abstract (2018):305-305, https://hdl.handle.net/21.15107/rcub_farfar_4894 .