Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• benzodioxepinones 12 in all cases (Scheme 11). The synthesized compounds demonstrated excellent drug-like features. Parkinson disease (PD) Knoevenagel–Michael addition/cyclization (MCR 3 + 2): Sirtuins, a group of enzymes that rely on NAD+ to function as protein deacetylases, have garnered attention across multiple

Synthesis and HDAC inhibitory activity of pyrimidine-based hydroxamic acids

• Virginija Jakubkiene,
• Gabrielius Ernis Valiulis,
• Markus Schweipert,
• Asta Zubriene,
• Daumantas Matulis,
• Franz-Josef Meyer-Almes and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 837–844, doi:10.3762/bjoc.18.84

• their catalytic site, while the remaining 7 isoforms of class III, known as sirtuins, are dependent on the NAD+ coenzyme [3][4]. According to current knowledge, HDAC inhibitors usually have several structural subunits: a zinc chelating group, a hydrophobic linker, and a hydrophobic (usually aromatic

Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors

• Christoph W. Grathwol,
• Nathalie Wössner,
• Sören Swyter,
• Adam C. Smith,
• Enrico Tapavicza,
• Robert K. Hofstetter,
• Anja Bodtke,
• Manfred Jung and
• Andreas Link

Beilstein J. Org. Chem. 2019, 15, 2170–2183, doi:10.3762/bjoc.15.214

• ‐time photomodulation of sirtuins in vitro. Keywords: azo compounds; epigenetics; photoswitch; sirtuins; stilbenes; Introduction Sirtuins are protein deacylases that cleave off not only acetyl, but also other acyl groups from the ε-amino group of lysines in histones and many other substrate proteins

• extended ageing in humans [13][14][15][16]. Regarding tumorigenesis, the knowledge on the influence of sirtuins is inconsistent. Sirt1, Sirt2 and Sirt3 all have been reported to act either as tumor suppressors or promotors, depending on the particular cell type [1][17]. The ability to externally control

• useful tools in the further investigation of the biochemistry and pharmacology of sirtuins. Results Chemistry of azastilbenes All azastilbene derivatives were synthesised by palladium-catalysed cross-coupling reactions using either commercially available 5-bromonicotinamide (3a) or methyl 5

Thioester derivatives of the natural product psammaplin A as potent histone deacetylase inhibitors

• Matthias G. J. Baud,
• Thomas Leiser,
• Vanessa Petrucci,
• Mekala Gunaratnam,
• Stephen Neidle,
• Franz-Josef Meyer-Almes and
• Matthew J. Fuchter

Beilstein J. Org. Chem. 2013, 9, 81–88, doi:10.3762/bjoc.9.11

• sirtuins) [5]. Class I HDACs (HDAC1, 2, 3, 8) are mostly present in the nucleus, whereas class II HDACs are tissue specific and shuttle between the cytoplasm and the nucleus [8][9]. Class II can be further subdivided into class IIa (HDAC4, 5, 7, 9) and class IIb (HDAC6, 10). HDAC11 constitutes its own

• class IV. Despite their name, several HDACs are able to deacetylate a number of nonhistone protein substrates [10][11]. Sirtuins are structurally and mechanistically distinct enzymes. To date, only two compounds that inhibit HDACs have been FDA approved: suberoylanilide hydroxamic acid (SAHA, 1, trade