Class I histone deacetylase inhibition by aryl butenoic acid derivatives: In silico and in vitro studies

Gamze Bora; Suat Sarı; Gülce Taşkor; Sevim Dalkara; Hayat Erdem Yurter

Class I histone deacetylase inhibition by aryl butenoic acid derivatives: In silico and in vitro studies

Abstract

Histone deacetylases (HDAC) are evolutionary conserved enzymes, which catalyze removal of acetyl groups from histone and non-histone proteins, therefore, control multiple biological processes. Inhibition of their activities have been investigated to modify gene expression and/or protein functions not only for treatment of certain diseases but also for understanding functions of deacetylase isoforms. We previously synthesized aryl butenoic acid derivatives and identified their pan-HDAC inhibition activities. In this study, we investigated selective inhibition activities of these derivatives (C1, C3, C4) on class I HDACs using in silico and in vitro approaches. Molecular docking studies of the three aryl butenoic acid derivatives were performed on the crystal structures of HDAC 1, 2, 3 and 8, which were obtained from RCSB protein databank, using Glide software. In vitro inhibition activities of the compounds at two different concentrations were tested using fluorometric assay. In silico results indicated that all the compounds showed higher affinity to HDAC 1 and 8 than other class I deacetylases. In vitro analysis showed that the compounds inhibit HDAC 8 more effectively than HDAC 1. It was shown that C1 had higher binding affinity and inhibition activity to both enzymes. We concluded that, C1 inhibited both HDAC 1 and 8, however, C3 and C4 showed slight selectivity for HDAC 8 over HDAC 1, which was in agreement with the docking studies. Further cell culture studies will be valuable to determine increased acetylation on target proteins in response to compound treatment.

Keywords

References

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Details

Primary Language

English

Subjects

Pharmaceutical Chemistry

Journal Section

Research Article

Authors

Gamze Bora ^*
Türkiye

Suat Sarı
Türkiye

Gülce Taşkor This is me
Türkiye

Sevim Dalkara
Türkiye

Hayat Erdem Yurter
Türkiye

Publication Date

June 27, 2025

Submission Date

May 29, 2019

Acceptance Date

July 10, 2019

Published in Issue

Year 2019 Volume: 23 Number: 5

IZ

https://izlik.org/JA29GX74PA

Cite

RIS / Bibtex

APA

Bora, G., Sarı, S., Taşkor, G., Dalkara, S., & Erdem Yurter, H. (2025). Class I histone deacetylase inhibition by aryl butenoic acid derivatives: In silico and in vitro studies. Journal of Research in Pharmacy, 23(5), 952-959. https://izlik.org/JA29GX74PA

AMA

1.Bora G, Sarı S, Taşkor G, Dalkara S, Erdem Yurter H. Class I histone deacetylase inhibition by aryl butenoic acid derivatives: In silico and in vitro studies. J. Res. Pharm. 2025;23(5):952-959. https://izlik.org/JA29GX74PA

Chicago

Bora, Gamze, Suat Sarı, Gülce Taşkor, Sevim Dalkara, and Hayat Erdem Yurter. 2025. “Class I Histone Deacetylase Inhibition by Aryl Butenoic Acid Derivatives: In Silico and in Vitro Studies”. Journal of Research in Pharmacy 23 (5): 952-59. https://izlik.org/JA29GX74PA.

EndNote

Bora G, Sarı S, Taşkor G, Dalkara S, Erdem Yurter H (July 1, 2025) Class I histone deacetylase inhibition by aryl butenoic acid derivatives: In silico and in vitro studies. Journal of Research in Pharmacy 23 5 952–959.

IEEE

[1]G. Bora, S. Sarı, G. Taşkor, S. Dalkara, and H. Erdem Yurter, “Class I histone deacetylase inhibition by aryl butenoic acid derivatives: In silico and in vitro studies”, J. Res. Pharm., vol. 23, no. 5, pp. 952–959, July 2025, [Online]. Available: https://izlik.org/JA29GX74PA

ISNAD

Bora, Gamze - Sarı, Suat - Taşkor, Gülce - Dalkara, Sevim - Erdem Yurter, Hayat. “Class I Histone Deacetylase Inhibition by Aryl Butenoic Acid Derivatives: In Silico and in Vitro Studies”. Journal of Research in Pharmacy 23/5 (July 1, 2025): 952-959. https://izlik.org/JA29GX74PA.

JAMA

1.Bora G, Sarı S, Taşkor G, Dalkara S, Erdem Yurter H. Class I histone deacetylase inhibition by aryl butenoic acid derivatives: In silico and in vitro studies. J. Res. Pharm. 2025;23:952–959.

MLA

Bora, Gamze, et al. “Class I Histone Deacetylase Inhibition by Aryl Butenoic Acid Derivatives: In Silico and in Vitro Studies”. Journal of Research in Pharmacy, vol. 23, no. 5, July 2025, pp. 952-9, https://izlik.org/JA29GX74PA.

Vancouver

1.Gamze Bora, Suat Sarı, Gülce Taşkor, Sevim Dalkara, Hayat Erdem Yurter. Class I histone deacetylase inhibition by aryl butenoic acid derivatives: In silico and in vitro studies. J. Res. Pharm. [Internet]. 2025 Jul. 1;23(5):952-9. Available from: https://izlik.org/JA29GX74PA