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

Victoria V. Lipson; Fedyr G. Yaremenko; Volodymyr M. Vakula; Svitlana V. Kovalenko; Alexander V. Kyrychenko; Sergiy M. Desenko; Petro О. Borysko; Sergiy O. Zozulya

doi:10.1055/s-0043-1763747

SynOpen, Inhaltsverzeichnis

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∗

^aState Institution ‘V. Ya. Danilevsky Institute for Endocrine Pathology Problems’, National Academy of Medical Sciences of Ukraine, Alchevsky St., 10, Kharkiv, 61002, Ukraine

^cV.N. Karazin Kharkiv National University, 4 Svobody Sq., Kharkiv, 61022, Ukraine

,

Fedyr G. Yaremenko

^aState 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

^aState Institution ‘V. Ya. Danilevsky Institute for Endocrine Pathology Problems’, National Academy of Medical Sciences of Ukraine, Alchevsky St., 10, Kharkiv, 61002, Ukraine

^bDivision of Chemistry of Functional Materials, State Scientific Institution ‘Institute for Single Crystals’ NAS of Ukraine, 60 Nauky Ave., Kharkiv, 61072, Ukraine

,

Svitlana V. Kovalenko

^bDivision of Chemistry of Functional Materials, State Scientific Institution ‘Institute for Single Crystals’ NAS of Ukraine, 60 Nauky Ave., Kharkiv, 61072, Ukraine

,

Alexander V. Kyrychenko

^bDivision of Chemistry of Functional Materials, State Scientific Institution ‘Institute for Single Crystals’ NAS of Ukraine, 60 Nauky Ave., Kharkiv, 61072, Ukraine

^cV.N. Karazin Kharkiv National University, 4 Svobody Sq., Kharkiv, 61022, Ukraine

,

Sergiy M. Desenko

^bDivision of Chemistry of Functional Materials, State Scientific Institution ‘Institute for Single Crystals’ NAS of Ukraine, 60 Nauky Ave., Kharkiv, 61072, Ukraine

,

Petro О. Borysko

^dENAMINE Ltd., Chervonotkatska str., 67, Kyiv, 02094, Ukraine

,

Sergiy O. Zozulya

^dENAMINE Ltd., Chervonotkatska str., 67, Kyiv, 02094, Ukraine

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Abstract

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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

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Referenzen

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