Tuning and predicting biological affinity: aryl nitriles as cysteine protease inhibitors
- 16 February 2012
- journal article
- research article
- Published by Royal Society of Chemistry (RSC) in Organic & Biomolecular Chemistry
- Vol. 10 (30) , 5764-5768
Abstract
A series of aryl nitrile-based ligands were prepared to investigate the effect of their electrophilicity on the affinity against the cysteine proteases rhodesain and human cathepsin L. Density functional theory calculations provided relative reactivities of the nitriles, enabling prediction of their biological affinity and cytotoxicity and a clear structure–activity relationship.Keywords
This publication has 23 references indexed in Scilit:
- Peptidomimetic nitriles as selective inhibitors for the malarial cysteine protease falcipain-2MedChemComm, 2011
- Quantification of the Electrophilic Reactivities of Aldehydes, Imines, and EnonesJournal of the American Chemical Society, 2011
- Emerging principles in protease-based drug discoveryNature Reviews Drug Discovery, 2010
- Nitrile-Containing Pharmaceuticals: Efficacious Roles of the Nitrile PharmacophoreJournal of Medicinal Chemistry, 2010
- Falcipain Inhibitors: Optimization Studies of the 2-Pyrimidinecarbonitrile Lead SeriesJournal of Medicinal Chemistry, 2010
- Crystal Structures of TbCatB and Rhodesain, Potential Chemotherapeutic Targets and Major Cysteine Proteases of Trypanosoma bruceiPLOS Neglected Tropical Diseases, 2010
- Vinyl Sulfones as Antiparasitic Agents and a Structural Basis for Drug DesignJournal of Biological Chemistry, 2009
- A generally applicable method for assessing the electrophilicity and reactivity of diverse nitrile-containing compoundsBioorganic & Medicinal Chemistry Letters, 2007
- Targeting proteases: successes, failures and future prospectsNature Reviews Drug Discovery, 2006
- Biological Roles of Proteases in Parasitic ProtozoaAnnual Review of Biochemistry, 2002