The investigation of drug repurposing for HDAC1 inhibitory effects by in silico and in vitro methods

Hüseyin İstanbullu; Ezgi Turunç; Sami Hamdoun; Merve Saylam; Halil Koyu; Tijen Kaya-temiz

Makale detayları

The investigation of drug repurposing for HDAC1 inhibitory effects by in silico and in vitro methods

Yazarlar:

Hüseyin İstanbullu | Ezgi Turunç | Sami Hamdoun | Merve Saylam | Halil Koyu | Tijen Kaya-temiz

Yayıncı:

Istanbul University

Ana Başlıklar:

Pharmacology and Pharmaceutical Sciences

Dergi:

İstanbul Journal of Pharmacy Vol.53 Issue 3, pp.287-293

Belge Tipi:

Makale

Yayın Tarihi:

12/2023

Belge Dili:

İngilizce

Document ID (Org No.):

2001311556

pISSN:

2587-2087

Anahtar kelimeler:

Özet:

 Background and Aims:Histone deacetylases HDACs modulate chromatin structure and regulate gene expression. The imbalance in chromatin acetylation and dysregulation of histone deacetylases are challenging in many pathologies, ranging from cancer to neurodegeneration. Computer-based in silico methods are becoming increasingly important in the determination of therapeutic targets and the development of personalized treatment approaches. This study aimed to investigate the HDAC1 inhibitory effects of chronic prescription drugs using in silico and in vitro methods. Methods:Five chronically used prescription drugs were chosen: ipratropium bromide, metoprolol, leflunomide, nateglinide, and levothyroxine. Molecular docking was performed for each of the chosen drugs as well as the known inhibitor Trichostatin A on HDAC1. The binding pose with the best scores was saved for each compound and analyzed for its interaction with the protein. An HDAC1 inhibitor screening assay kit was used to determine the IC50 value for each drug. Results:The IC50 values for HDAC1 inhibition by ipratropium bromide, metoprolol, leflunomide, nateglinide, and levothyroxine were found to be 352.10 μM, 255.70 μM, 219.80 μM, 289.50 μM, and 132.70 μM, respectively, whereas the value for the positive control Trichostatin A was 36.13 nM. GraphPad Prism 5 was used to conduct statistical analyses. Conclusion:In this study, the in vitro HDAC1 inhibitory effect of ipratropium bromide, metoprolol, leflunomide, nateglinide, and levothyroxine is shown for the first time. In silico and in vitro methodologies used to show HDAC1 inhibitory activity in marketed drugs can provide insight into new drug discovery studies against cancer or neurodegenerative diseases.

 Background and Aims:Histone deacetylases HDACs modulate chromatin structure and regulate gene expression. The imbalance in chromatin acetylation and dysregulation of histone deacetylases are challenging in many pathologies, ranging from cancer to neurodegeneration. Computer-based in silico methods are becoming increasingly important in the determination of therapeutic targets and the development of personalized treatment approaches. This study aimed to investigate the HDAC1 inhibitory effects of chronic prescription drugs using in silico and in vitro methods. Methods:Five chronically used prescription drugs were chosen: ipratropium bromide, metoprolol, leflunomide, nateglinide, and levothyroxine. Molecular docking was performed for each of the chosen drugs as well as the known inhibitor Trichostatin A on HDAC1. The binding pose with the best scores was saved for each compound and analyzed for its interaction with the protein. An HDAC1 inhibitor screening assay kit was used to determine the IC50 value for each drug. Results:The IC50 values for HDAC1 inhibition by ipratropium bromide, metoprolol, leflunomide, nateglinide, and levothyroxine were found to be 352.10 μM, 255.70 μM, 219.80 μM, 289.50 μM, and 132.70 μM, respectively, whereas the value for the positive control Trichostatin A was 36.13 nM. GraphPad Prism 5 was used to conduct statistical analyses. Conclusion:In this study, the in vitro HDAC1 inhibitory effect of ipratropium bromide, metoprolol, leflunomide, nateglinide, and levothyroxine is shown for the first time. In silico and in vitro methodologies used to show HDAC1 inhibitory activity in marketed drugs can provide insight into new drug discovery studies against cancer or neurodegenerative diseases.

 Background and Aims:Histone deacetylases HDACs modulate chromatin structure and regulate gene expression. The imbalance in chromatin acetylation and dysregulation of histone deacetylases are challenging in many pathologies, ranging from cancer to neurodegeneration. Computer-based in silico methods are becoming increasingly important in the determination of therapeutic targets and the development of personalized treatment approaches. This study aimed to investigate the HDAC1 inhibitory effects of chronic prescription drugs using in silico and in vitro methods. Methods:Five chronically used prescription drugs were chosen: ipratropium bromide, metoprolol, leflunomide, nateglinide, and levothyroxine. Molecular docking was performed for each of the chosen drugs as well as the known inhibitor Trichostatin A on HDAC1. The binding pose with the best scores was saved for each compound and analyzed for its interaction with the protein. An HDAC1 inhibitor screening assay kit was used to determine the IC50 value for each drug. Results:The IC50 values for HDAC1 inhibition by ipratropium bromide, metoprolol, leflunomide, nateglinide, and levothyroxine were found to be 352.10 μM, 255.70 μM, 219.80 μM, 289.50 μM, and 132.70 μM, respectively, whereas the value for the positive control Trichostatin A was 36.13 nM. GraphPad Prism 5 was used to conduct statistical analyses. Conclusion:In this study, the in vitro HDAC1 inhibitory effect of ipratropium bromide, metoprolol, leflunomide, nateglinide, and levothyroxine is shown for the first time. In silico and in vitro methodologies used to show HDAC1 inhibitory activity in marketed drugs can provide insight into new drug discovery studies against cancer or neurodegenerative diseases.

 Background and Aims:Histone deacetylases HDACs modulate chromatin structure and regulate gene expression. The imbalance in chromatin acetylation and dysregulation of histone deacetylases are challenging in many pathologies, ranging from cancer to neurodegeneration. Computer-based in silico methods are becoming increasingly important in the determination of therapeutic targets and the development of personalized treatment approaches. This study aimed to investigate the HDAC1 inhibitory effects of chronic prescription drugs using in silico and in vitro methods. Methods:Five chronically used prescription drugs were chosen: ipratropium bromide, metoprolol, leflunomide, nateglinide, and levothyroxine. Molecular docking was performed for each of the chosen drugs as well as the known inhibitor Trichostatin A on HDAC1. The binding pose with the best scores was saved for each compound and analyzed for its interaction with the protein. An HDAC1 inhibitor screening assay kit was used to determine the IC50 value for each drug. Results:The IC50 values for HDAC1 inhibition by ipratropium bromide, metoprolol, leflunomide, nateglinide, and levothyroxine were found to be 352.10 μM, 255.70 μM, 219.80 μM, 289.50 μM, and 132.70 μM, respectively, whereas the value for the positive control Trichostatin A was 36.13 nM. GraphPad Prism 5 was used to conduct statistical analyses. Conclusion:In this study, the in vitro HDAC1 inhibitory effect of ipratropium bromide, metoprolol, leflunomide, nateglinide, and levothyroxine is shown for the first time. In silico and in vitro methodologies used to show HDAC1 inhibitory activity in marketed drugs can provide insight into new drug discovery studies against cancer or neurodegenerative diseases.

Makale detayları

The investigation of drug repurposing for HDAC1 inhibitory effects by in silico and in vitro methods

Yazarlar:

Hüseyin İstanbullu | Ezgi Turunç | Sami Hamdoun | Merve Saylam | Halil Koyu | Tijen Kaya-temiz

Yayıncı:

Istanbul University

Ana Başlıklar:

Pharmacology and Pharmaceutical Sciences

Dergi:

İstanbul Journal of Pharmacy Vol.53 Issue 3, pp.287-293

Belge Tipi:

Makale

Yayın Tarihi:

12/2023

Belge Dili:

İngilizce

Document ID (Org No.):

2001311556

pISSN:

2587-2087

Docking

drug repurposing

HDAC1

in silico

molecular modeling

Sayı

Makale detayları

The investigation of drug repurposing for HDAC1 inhibitory effects by in silico and in vitro methods

Yazarlar: Hüseyin İstanbullu | Ezgi Turunç | Sami Hamdoun | Merve Saylam | Halil Koyu | Tijen Kaya-temiz

Yayıncı: Istanbul University

Ana Başlıklar: Pharmacology and Pharmaceutical Sciences

Dergi: İstanbul Journal of Pharmacy Vol.53 Issue 3, pp.287-293

Belge Tipi: Makale

Yayın Tarihi: 12/2023

Belge Dili: İngilizce

Document ID (Org No.): 2001311556

pISSN: 2587-2087

Docking

drug repurposing

HDAC1

in silico

molecular modeling

Sayı

Yazarlar:

Hüseyin İstanbullu | Ezgi Turunç | Sami Hamdoun | Merve Saylam | Halil Koyu | Tijen Kaya-temiz

Yayıncı:

Istanbul University

Ana Başlıklar:

Pharmacology and Pharmaceutical Sciences

Dergi:

İstanbul Journal of Pharmacy Vol.53 Issue 3, pp.287-293

Belge Tipi:

Makale

Yayın Tarihi:

12/2023

Belge Dili:

İngilizce

Document ID (Org No.):

2001311556

pISSN:

2587-2087