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

İstanbullu Hüseyin; Turunc Ezgi; Hamdoun Sami; Saylam Merve; Koyu Halil; Kaya Temiz Tĳen

doi:https://dx.doi.org/10.26650/IstanbulJPharm.2023.1269175

Araştırma Makalesi

DOI :10.26650/IstanbulJPharm.2023.1269175 IUP :10.26650/IstanbulJPharm.2023.1269175 Tam Metin (PDF)

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

Hüseyin İstanbullu, Ezgi Turunc, Sami Hamdoun, Merve Saylam, Halil Koyu, Tĳen Kaya Temiz

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.

Anahtar Kelimeler: Docking, drug repurposing, HDAC1, in silico, molecular modeling

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APA

İstanbullu, H., Turunc, E., Hamdoun, S., Saylam, M., Koyu, H., & Kaya Temiz, T. (2023). The investigation of drug repurposing for HDAC1 inhibitory effects by in silico and in vitro methods. İstanbul Journal of Pharmacy, 53(3), 287-293. https://doi.org/10.26650/IstanbulJPharm.2023.1269175

AMA

İstanbullu H, Turunc E, Hamdoun S, Saylam M, Koyu H, Kaya Temiz T. The investigation of drug repurposing for HDAC1 inhibitory effects by in silico and in vitro methods. İstanbul Journal of Pharmacy. 2023;53(3):287-293. https://doi.org/10.26650/IstanbulJPharm.2023.1269175

ABNT

İstanbullu, H.; Turunc, E.; Hamdoun, S.; Saylam, M.; Koyu, H.; Kaya Temiz, T. The investigation of drug repurposing for HDAC1 inhibitory effects by in silico and in vitro methods. İstanbul Journal of Pharmacy, [Publisher Location], v. 53, n. 3, p. 287-293, 2023.

Chicago: Author-Date Style

İstanbullu, Hüseyin, and Ezgi Turunc and Sami Hamdoun and Merve Saylam and Halil Koyu and Tĳen Kaya Temiz. 2023. “The investigation of drug repurposing for HDAC1 inhibitory effects by in silico and in vitro methods.” İstanbul Journal of Pharmacy 53, no. 3: 287-293. https://doi.org/10.26650/IstanbulJPharm.2023.1269175

Chicago: Humanities Style

İstanbullu, Hüseyin, and Ezgi Turunc and Sami Hamdoun and Merve Saylam and Halil Koyu and Tĳen Kaya Temiz. “The investigation of drug repurposing for HDAC1 inhibitory effects by in silico and in vitro methods.” İstanbul Journal of Pharmacy 53, no. 3 (May. 2024): 287-293. https://doi.org/10.26650/IstanbulJPharm.2023.1269175

Harvard: Australian Style

İstanbullu, H & Turunc, E & Hamdoun, S & Saylam, M & Koyu, H & Kaya Temiz, T 2023, 'The investigation of drug repurposing for HDAC1 inhibitory effects by in silico and in vitro methods', İstanbul Journal of Pharmacy, vol. 53, no. 3, pp. 287-293, viewed 8 May. 2024, https://doi.org/10.26650/IstanbulJPharm.2023.1269175

Harvard: Author-Date Style

İstanbullu, H. and Turunc, E. and Hamdoun, S. and Saylam, M. and Koyu, H. and Kaya Temiz, T. (2023) ‘The investigation of drug repurposing for HDAC1 inhibitory effects by in silico and in vitro methods’, İstanbul Journal of Pharmacy, 53(3), pp. 287-293. https://doi.org/10.26650/IstanbulJPharm.2023.1269175 (8 May. 2024).

MLA

İstanbullu, Hüseyin, and Ezgi Turunc and Sami Hamdoun and Merve Saylam and Halil Koyu and Tĳen Kaya Temiz. “The investigation of drug repurposing for HDAC1 inhibitory effects by in silico and in vitro methods.” İstanbul Journal of Pharmacy, vol. 53, no. 3, 2023, pp. 287-293. [Database Container], https://doi.org/10.26650/IstanbulJPharm.2023.1269175

Vancouver

İstanbullu H, Turunc E, Hamdoun S, Saylam M, Koyu H, Kaya Temiz T. The investigation of drug repurposing for HDAC1 inhibitory effects by in silico and in vitro methods. İstanbul Journal of Pharmacy [Internet]. 8 May. 2024 [cited 8 May. 2024];53(3):287-293. Available from: https://doi.org/10.26650/IstanbulJPharm.2023.1269175 doi: 10.26650/IstanbulJPharm.2023.1269175

ISNAD

İstanbullu, Hüseyin - Turunc, Ezgi - Hamdoun, Sami - Saylam, Merve - Koyu, Halil - Kaya Temiz, Tĳen. “The investigation of drug repurposing for HDAC1 inhibitory effects by in silico and in vitro methods”. İstanbul Journal of Pharmacy 53/3 (May. 2024): 287-293. https://doi.org/10.26650/IstanbulJPharm.2023.1269175

Cilt 53, Sayı 32023, S. 287-293

ZAMAN ÇİZELGESİ

Gönderim	23.03.2023
Kabul	25.09.2023
Çevrimiçi Yayınlanma	28.11.2023

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İstanbul Journal of Pharmacy

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

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APA

AMA

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Chicago: Author-Date Style

Chicago: Humanities Style

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MLA

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