Tetrasubstituted Pyrrole Derivative Mimetics of Protein-Protein Interaction Hot-Spot Residues: A Promising Class of Anticancer Agents Targeting Melanoma Cells.

ABSTRACT: A new series of tetrasubstituted pyrrole derivatives (TSPs) was synthesized based on a previously developed hypothesis on their ability to mimic hydrophobic protein motifs. The resulting new TSPs were endowed with a significant toxicity against human epithelial melanoma A375 cells, showing IC₅₀ values ranging from 10 to 27 μM, consistent with the IC₅₀ value of the reference compound nutlin-3a (IC₅₀ = 15 μM). In particular, compound 10a (IC₅₀ = 10 μM) resulted as both the most soluble and active among the previous and present TSPs. The biological investigation evidenced that the anticancer activity is related to the activation of apoptotic cell-death pathways, supporting our rational design based on the ability of TSPs to interfere with PPI

SUBMITTER: Persico M 

PROVIDER: S-EPMC10223356 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature