ABSTRACT
Aim: Encouraged by the antitumor activity exhibited by triazolylpeptidyl penicillins, we decided to synthesize and evaluate a library of peptoid analogs. Results: The replacement of the dipeptide unit of the reference compound, TAP7f, was investigated. In addition, the effect of the triazole linking group on the biological activity of these new derivatives was evaluated, exchanging it with a glycine spacer. The cytotoxic effect of the library compounds was determined in the B16-F0 cell line and compared with the effects on normal murine mammary gland cells. Conclusion: Among the tested compounds, peptoid 4e exhibited the highest antiproliferative activity.
Subject(s)
Antineoplastic Agents/pharmacology , Drug Design , Penicillins/pharmacology , Peptoids/pharmacology , Triazoles/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Mice , Molecular Conformation , Penicillins/chemical synthesis , Penicillins/chemistry , Peptoids/chemical synthesis , Peptoids/chemistry , Triazoles/chemical synthesis , Triazoles/chemistry , Tumor Cells, CulturedABSTRACT
Herein we describe a versatile approach for the synthesis of acylhydrazino-peptomers, a new class of peptidomimetics. The key idea in this approach is based on a simple route using a one-pot hydrazino-Ugi four-component reaction followed by a hydrazinolysis or hydrolysis reaction and subsequent hydrazino-Ugi reaction or classical Ugi reaction for the construction of acyclic acylhydrazino-peptomers. The consecutive multicomponent reactions produced a variety of acylhydrazino-peptomers in moderate to excellent yields (47-90%). These compounds are multifunctional intermediates that can be further functionalized to obtain new peptidomimetics with potential biological activity.