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CC BY 4.0 · SynOpen 2024; 08(02): 100-108
DOI: 10.1055/s-0043-1763747
paper

Discovery of Novel N-Acylhydrazone Derivatives as Potent Inhibitors of Sirtuin-1

Victoria V. Lipson∗
a   State Institution ‘V. Ya. Danilevsky Institute for Endocrine Pathology Problems’, National Academy of Medical Sciences of Ukraine, Alchevsky St., 10, Kharkiv, 61002, Ukraine
c   V.N. Karazin Kharkiv National University, 4 Svobody Sq., Kharkiv, 61022, Ukraine
,
Fedyr G. Yaremenko
a   State Institution ‘V. Ya. Danilevsky Institute for Endocrine Pathology Problems’, National Academy of Medical Sciences of Ukraine, Alchevsky St., 10, Kharkiv, 61002, Ukraine
,
Volodymyr M. Vakula
a   State Institution ‘V. Ya. Danilevsky Institute for Endocrine Pathology Problems’, National Academy of Medical Sciences of Ukraine, Alchevsky St., 10, Kharkiv, 61002, Ukraine
b   Division of Chemistry of Functional Materials, State Scientific Institution ‘Institute for Single Crystals’ NAS of Ukraine, 60 Nauky Ave., Kharkiv, 61072, Ukraine
,
Svitlana V. Kovalenko
b   Division of Chemistry of Functional Materials, State Scientific Institution ‘Institute for Single Crystals’ NAS of Ukraine, 60 Nauky Ave., Kharkiv, 61072, Ukraine
,
Alexander V. Kyrychenko
b   Division of Chemistry of Functional Materials, State Scientific Institution ‘Institute for Single Crystals’ NAS of Ukraine, 60 Nauky Ave., Kharkiv, 61072, Ukraine
c   V.N. Karazin Kharkiv National University, 4 Svobody Sq., Kharkiv, 61022, Ukraine
,
Sergiy M. Desenko
b   Division of Chemistry of Functional Materials, State Scientific Institution ‘Institute for Single Crystals’ NAS of Ukraine, 60 Nauky Ave., Kharkiv, 61072, Ukraine
,
Petro О. Borysko
d   ENAMINE Ltd., Chervonotkatska str., 67, Kyiv, 02094, Ukraine
,
Sergiy O. Zozulya
d   ENAMINE Ltd., Chervonotkatska str., 67, Kyiv, 02094, Ukraine
› Author AffiliationsThe authors acknowledge the National Academy of Science of Ukraine for financial support under the project 0122U001857 and the National Academy of Medical Science of Ukraine for financial support under the project 0121U111536.
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Abstract

SIRT1 enzyme is a key family member of Silent Information Regulators (Sirtuins), which catalyze the deacetylation of proteins. Therefore, developing new SIRT1 inhibitors has potential application in treating cancer disease and age-related metabolic disorders. In this study, we synthesized a series of N-acylhydrazone (NAH) derivatives and performed high-throughput screening of their inhibitory activity against the recombinant SIRT1 protein by a luminescent assay. Using in silico screening, we identified a new NAH derivative that features both selectivity and a high binding affinity towards the active pocket of SIRT1 that are comparable to known inhibitors such as Ex527 and Sirtinol. Such high binding affinity makes the new derivatives promising alternatives to the available inhibitors and holds promise for developing better-targeted drugs against SIRT1 activity.

Key words

Sirtuin1 - organic synthesis - N-acylhydrazone - inhibitors - molecular docking

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0043-1763747.
  • Supporting Information


Publication History

Received: 12 November 2023

Accepted: 11 March 2024

Article published online:
04 April 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by/4.0/)

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