Targeting of the Leishmania mexicana cysteine protease CPB2.8ΔCTE by decorated fused benzo[b]thiophene scaffold. Issue 36 (23rd March 2016)

• Record Type: Journal Article
• Authors: Scala, A.; Micale, N.; Piperno, A.; Rescifina, A.; Schirmeister, T.; Kesselring, J.; Grassi, G.
• Is Part Of: RSC advances. Volume 6:Issue 36(2016)
• Page Start: 30628
• Page End: 30635
• Publication Date: 2016-03-23
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c6ra05557e
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : A potent and highly selective anhydride-based inhibitor of Leishmania mexicana cysteine protease CPB2.8 (IC50 = 3.7 μM) was investigated by inhibition assays, NMR biomimetic experiments and docking studies. Abstract : A potent and highly selective anhydride-based inhibitor of Leishmania mexicana cysteine protease CPB2.8ΔCTE (IC50 = 3.7 μM) was identified. The details of the interaction of the ligand with the enzyme active site were investigated by NMR biomimetic experiments and docking studies. Results of inhibition assays, NMR and theoretical studies indicate that the ligand acts initially as a non-covalent inhibitor and later as an irreversible covalent inhibitor by chemoselective attack of CYS 25 thiolate to an anhydride carbonyl.