Structures and Bioactivities of Dihydrochalcones from Metrodorea stipularis

Abstract

Metrodorea stipularis stem extracts were studied in the search for possible antichagastic, antimalarial, and antitumoral compounds using cruzain from Trypanosoma cruzi, Plasmodium falciparum, and cathepsins B and L, as molecular targets, respectively. Dihydrochalcones 1, 2, 3, and 4 showed significant inhibitory activity against all the targets. Compounds 1-4 displayed IC50 values ranging from 7.7 to 21.6 μM against cruzain; dihydrochalcones 2 and 4 inhibited the growth of three different strains of P. falciparum in low micromolar concentrations; and against cathepsins B and L these compounds presented good inhibitory activity with IC50 values ranging from 1.0 to 14.9 μM. The dihydrochalcones showed good selectivity in their inhibitory activities against the cysteine proteases.

Identification of Interleukin-8-Reducing Lead Compounds Based on SAR Studies on Dihydrochalcone-Related Compounds in Human Gingival Fibroblasts (HGF-1 cells) In Vitro

“…The chosen compounds share close structural similarities but show differences in their anti-inflammatory properties, which might be explained by different molecular mechanisms of action. For selected naturally occurring dihydrochalcones, a direct molecular interaction with cathepsins, enzymes involved in inflammation and metabolic disorders [32], has already been established by Burger et al [33]. Future studies could, therefore, focus on this direct interaction.…”

Secondary Metabolites From Pachystroma Longifolium (Nees) I. M. Johnst (Euphorbiaceae) and Evaluation of Its Extracts as Cathepsins Inhibitors

“…Four dihydrochalcones were tested against cathepsins B and L and these compounds presented good inhibitory activity with IC 50 values ranging from 1.0 to 14.9 μM. These compounds also showed good selectivity in their inhibitory activities against the cysteine proteases 19 . Both crude extract and active fractions provided by leaves of Pachystroma longifolium were able to inhibit cat-K, -L and -V in higher concentrations.…”

Novel Non-Peptide Inhibitors against SmCL1 of Schistosoma mansoni: In Silico Elucidation, Implications and Evaluation via Knowledge Based Drug Discovery

“…Considering the above fact, cruzain non-peptide inhibitors were tested against SmCL1 via docking protocol to estimate the interaction energy and inhibition constant parameters. The parameters obtained were used to analyse the inhibition pattern by comparing it with the reported cruzain inhibition values [ 62 – 65 ].…”

“…As evident from the AutoDock results ( S4 Table ), non-peptide phytochemical inhibitors exhibit more negative interaction energy (> -7.00 Kcal/mol) and lower inhibition constant (< 10μM) against SmCL1 as in case of cruzain with lower reported IC50 values [ 62 ]. Further, AutoDock results for non-peptide non-phytochemical inhibitors ( S4 Table ) showed that Nequimed, thiazolidinones and thiosemicarbazone inhibitors exhibit less negative interaction energy (< -7.00 Kcal/mol) and higher inhibition constant (> 10μM) against SmCL1, which is in consistence with the reported cruzain inhibition parameters [ 63 – 65 ].…”