Tier 3 — preclinical

Lead Optimization: Synthesis and Biological Evaluation of Griseofulvin Derivatives as Novel SIRT6 Activators

Tilen Zorko, Jan Kogovšek, Luka Ciber, Ivana Ostojić, Nenad Maraš, Marko Novinec, Bogdan Štefane
ACS Medicinal Chemistry Letters 2026 17(3):662-669

Bibliography

PubMed
PMID 41847663
PubMed Central
PMC12989997
DOI
10.1021/acsmedchemlett.5c00690
Funding
Funded by Virella d.o.o.; the work was conducted at the Faculty of Chemistry and Chemical Technology, University of Ljubljana.
Competing interests
The authors declared no competing financial interest.

Study snapshot

DesignMedicinal-chemistry synthesis and biochemical SIRT6 activation study.
ModelPurified-enzyme and histone deacetylation assays.
SampleNot applicable; biochemical experiments.
InterventionGriseofulvin, forvisirvat and synthesized griseofulvin derivatives.
DurationNot applicable.
EndpointsSIRT6 activation fold change; dose-response behavior; H3K9 deacetylation; structure-activity relationships

What the study showed, in plain terms

This 2026 medicinal-chemistry paper expands the synthetic SIRT6 activator landscape around griseofulvin and forvisirvat. Several analogues retained strong activity at lower concentrations.

Key findings

Griseofulvin activated SIRT6 in the biochemical assay, while selected oxadiazole-containing analogues achieved stronger activation and better low-concentration activity.

What this study can and cannot tell us

Biochemical potency does not equal clinical efficacy, and these analogues are research compounds rather than established supplements or medicines.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability