Recent Advances in the Discovery of SIRT1/2 Inhibitors via Computational Methods: A Perspective

Area of Science:

• Biochemistry and Molecular Biology
• Medicinal Chemistry
• Computational Biology

Background:

• Sirtuins (SIRTs) are class III histone deacetylases (HDACs) involved in critical biological pathways like transcription, metabolism, and genome stability.
• Dysregulation of SIRTs is implicated in various diseases, including cancer, neurodegenerative disorders, diabetes, and cardiovascular and autoimmune diseases.
• Structural data of SIRT-ligand complexes have facilitated the development of targeted modulators.

Purpose of the Study:

• To review recent structure-based methods and ligands for identifying novel and selective sirtuin 1 and 2 (SIRT1/2) modulators.
• To provide a comprehensive perspective on computational approaches for discovering SIRT1/2 inhibitors (SIRTIs).
• To highlight significant SIRTIs reported in the literature since 2017.

Main Methods:

• Literature review of computational approaches and identified SIRT1/2 inhibitors.
• Analysis of structural data for SIRT-ligand complexes.
• Data collection from major scientific databases (SciFinder, Web of Science, Scopus, Google Scholar, PubMed) using specific keywords.

Main Results:

• Identification and discussion of successful computational strategies for SIRT1/2 inhibitor discovery.
• Presentation of promising SIRTIs that have emerged in recent scientific literature (post-2017).
• Emphasis on the diversity of ligands and structure-based methods employed.

Conclusions:

• Computational and structure-based approaches are effective in identifying novel SIRT1/2 modulators.
• Recent advancements have yielded promising SIRTIs with potential therapeutic applications.
• Continued research into SIRT modulators is crucial for addressing diseases associated with SIRT dysregulation.