Chalcones, semicarbazones and pyrazolines as inhibitors of cathepsins B, H and L

Abstract

Cathepsin B [EC 3.4.22.1], cathepsin H [EC 3.4.22.16] and cathepsin L [EC 3.4.22.15] are the most versatile lysosomal cysteine proteases and are responsible for intracellular protein degradation. These are involved in a number of pathological conditions including tissue degenerative processes. In the present work, we report the synthesis and systematic evaluation of differently substituted chalcones, chalconesemicarbazones, and diarylpyrazolines on cathepsins B, H and L activity. It was found that after a preliminary screening as cysteine protease inhibitors, chalconesemicarbazones were better inhibitors to these cysteine proteases than diarylpyrazolines followed by chalcones. All the synthesized compounds were identified as the best inhibitors to cathepsin L followed by cathepsin B and then cathepsin H. The results are compared with docking studies and it was found that all the compounds resulted in decrease in energy while interacting with the active site of the enzyme.

In-silico Recognition of Liquorice Phytoconstituents Specially Glabranin B as a Potential Cathepsin L Inhibitor to Hinder 2019-NCOV Host Cell Entry

“…The specific pocket of cathepsin L in which the active hits were bound contained polar amino acids like Gln19, Asp162 and Hie163. These findings were in agreement with the previously published results 14 The most active compound Glabranin B was bound through hydrogen bonding with Gln21, Asp 160 and Asp162 and through charged negative interactions with Glu159. Numerous hydrophobic interactions were observed with Cys22, Cys25, Leu69, Thr72, Ala135, Ala214, Ala215, and Phe143.…”

“…A rat study suggested that rectal or nasal administration of glycyrrhizin yielded 10-or 26-times, respectively, improvement in the bioavailability of the licorice saponin as compared with p.o. administration 14 . In addition, several sodium fatty acids were found to be the absorption enhancers for glycyrrhizin.…”

Lipophilicity as a Central Component of Drug-Like Properties of Chalchones and Flavonoid Derivatives

“…Thiazole chalcones, flavanones, flavones, 3-hydroxyflavones, and their acetylated derivatives have been previously synthesized by us. Thiazole chalcones were obtained by Claisen-Schmidt condensation of thiazole aldehydes with substituted acetophenones in ortho and/or para positions with hydroxy or methoxy groups [32]. By the cyclization of ortho hydroxychalcones with concentrated sulphuric acid [33], sodium acetate [34], or glacial acetic acid [35], the corresponding thiazole flavanones were synthesized .…”

Heterocycles 43. Synthesis, Characterization and Antioxidant Activity of Some Thiazole Hydroxychalcones and Their Flavonoidic Derivatives

“…The synthesis of thiazole hydroxychalcones 3a-h (Table I) was performed by Claisen-Schmidt condensation [14,18], starting from equimolar amounts of the previously obtained thiazole aldehydes 1a-d and the acetophenones substituted with a hydroxyl group in ortho or para position (Figure 2). The reaction was catalysed by potassium hydroxide [14].…”