Pyrrolo[3,4-c]quinoline-1,3-diones as potent caspase-3 inhibitors. Synthesis and SAR of 2-substituted 4-methyl-8-(morpholine-4-sulfonyl)-pyrrolo[3,4-c]quinoline-1,3-diones

Кравченко, Д. В.; Kysil, Volodymyr; Ткаченко, С. Е.; Maliarchouk, Sergey; Okun, Ilya; Ivachtchenko, Alexandre V.

doi:10.1016/j.ejmech.2005.07.011

Cited by 60 publications

(18 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, it was demonstrated that the most active substituents in the R3 region are 1,3,5-trimethyl-1 H -pyrazol and pyridine. 354 This last step of optimization resulted in finding two caspase-3 inhibitors 422 and 423 with nanomolar potency. This group of quinoline based inhibitors seems to be very promising not only for enzyme assays but also for in vivo studies (Figure 30).…”

Section: Caspase Inhibitorsmentioning

confidence: 99%

Small Molecule Active Site Directed Tools for Studying Human Caspases

et al. 2015

View full text Add to dashboard Cite

Caspases are proteases of clan CD and were described for the first time more than two decades ago. They play critical roles in the control of regulated cell death pathways including apoptosis and inflammation. Due to their involvement in the development of various diseases like cancer, neurodegenerative diseases or autoimmune disorders, caspases have been intensively investigated as potential drug targets, both in academic and industrial laboratories. This review presents a thorough, deep, and systematic assessment of all technologies developed over the years for the investigation of caspase activity and specificity using substrates and inhibitors, as well as activity based probes, which in recent years have attracted considerable interest due to their usefulness in the investigation of biological functions of this family of enzymes.

show abstract

Section: Caspase Inhibitorsmentioning

confidence: 99%

Small Molecule Active Site Directed Tools for Studying Human Caspases

et al. 2015

View full text Add to dashboard Cite

show abstract

“…24,25 Numerous small molecules and peptides that are inhibitors of caspases-3 have been synthesized. [26][27][28][29][30][31] Cells from certain types of cancerous tissues have elevated concentrations of pCasp-3. A study of primary isolates from 20 individuals with colon cancer, showed that on average, pCasp-3 is elevated six-fold in such isolates relative to adjacent noncancerous tissue.…”

Section: Procaspase-3 and Caspase-3mentioning

confidence: 99%

ortho-Formylation of oxygenated phenols

Akselsen

Skattebøl

Hansen

2009

Tetrahedron Letters

View full text Add to dashboard Cite

“…These include isatins, [78,79] indole aspartyl ketones, fuchsone derivatives, and pyrrolo [3,4-c]quinolone-1,3-diones [80].…”

Section: Active Site Inhibitorsmentioning

confidence: 99%

Caspases – Key Players in Apoptosis

Cade

Clark

2015

Proteases in Apoptosis: Pathways, Protocols and Translational Advances

View full text Add to dashboard Cite

Caspases are the terminal proteases involved in apoptosis, as well as being involved in inflammation. The apoptotic caspases can be classified as either initiator or effector caspases based on both their position in the caspase cascade and their activation mechanism. Initiator caspases require dimerization to be activated, and cleavage of a loop called the intersubunit linker stabilizes the active enzyme. Effector caspases, on the other hand, are found as dimers in the cell and cleavage of the intersubunit linker is the key step in their activation.The name caspase is short for cysteinyl aspartate-specific protease. As their name suggests, these enzymes hydrolyze peptide bonds after certain aspartate residues using a catalytic cysteine (with the aid of an active-site histidine residue). Caspases can be inhibited by endogenous inhibitors such as XIAP, by synthetic inhibitors which target either the active site or an allosteric site, or by post-translational modification. Further research is needed to find novel activators and inhibitors of caspases to treat diseases which involve misregulation of apoptosis.

show abstract

Pyrrolo[3,4-c]quinoline-1,3-diones as potent caspase-3 inhibitors. Synthesis and SAR of 2-substituted 4-methyl-8-(morpholine-4-sulfonyl)-pyrrolo[3,4-c]quinoline-1,3-diones

Cited by 60 publications

References 12 publications

Small Molecule Active Site Directed Tools for Studying Human Caspases

Small Molecule Active Site Directed Tools for Studying Human Caspases

ortho-Formylation of oxygenated phenols

Caspases – Key Players in Apoptosis

Contact Info

Product

Resources

About