Stucchi, M.Cairati, S.Cetin-Atalay, R.Christodoulou, M.S.Grazioso G.Pescitelli G.Silvani, A.Yildirim, D.C.Lesma G.2016-02-082016-02-08201514770520http://hdl.handle.net/11693/21970The concurrent employment of α-amino acid-derived chiral components such as aldehydes and α-isocyanoacetates, in a sequential Ugi reaction/cyclization two-step strategy, opens the door to the synthesis of three structurally distinct piperazine-based scaffolds, characterized by the presence of l-Ala and/or l-Phe-derived side chains and bearing appropriate functionalities to be easily applied in peptide chemistry. By means of computational studies, these scaffolds have been demonstrated to act as minimalist peptidomimetics, able to mimic a well defined range of peptide secondary structures and therefore potentially useful for the synthesis of small-molecule PPI modulators. Preliminary biological evaluation of two different resistant hepatocellular carcinoma cellular lines, for which differentiation versus resistance ability seem to be strongly correlated with well defined types of PPIs, has revealed a promising antiproliferative activity for selected compounds. © The Royal Society of Chemistry 2015.EnglishAmino acidsChemical reactionsMobile securityPeptidesStereochemistryAlpha-amino acidsAnti-proliferative activitiesBiological evaluationComputational studiesHepatocellular carcinomaPeptide chemistriesPeptide secondary structuresSmall moleculesSynthesis (chemical)alaninepeptidomimetic agentphenylalaninepiperazinepiperazine derivativecell differentiationcell proliferationchemistryconformationcyclizationdose responsedrug effectshumanquantum theorystructure activity relationsynthesistumor cell lineAlanineCell DifferentiationCell Line, TumorCell ProliferationCyclizationDose-Response Relationship, DrugHumansMolecular ConformationPeptidomimeticsPhenylalaninePiperazinesQuantum TheoryStructure-Activity RelationshipArticle10.1039/c5ob00218d