RESUMEN
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.
Asunto(s)
Antineoplásicos/farmacología , Diseño de Fármacos , Penicilinas/farmacología , Peptoides/farmacología , Triazoles/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Ratones , Conformación Molecular , Penicilinas/síntesis química , Penicilinas/química , Peptoides/síntesis química , Peptoides/química , Triazoles/síntesis química , Triazoles/química , Células Tumorales CultivadasRESUMEN
A combined organocatalytic and multicomponent synthetic approach was designed for the preparation of selenium-based peptoids and peptide-peptoid conjugates. This single-step synthetic protocol comprises the organocatalytic asymmetric insertion of phenylselenium in the aldehyde moiety followed by the Ugi four-component reaction which results in obtaining the desired compounds in good-to-moderate yields and with good-to-excellent levels of stereoselectivity.
Asunto(s)
Técnicas de Química Sintética , Fenómenos Químicos Orgánicos , Peptoides/síntesis química , Selenio , Espectroscopía de Resonancia MagnéticaRESUMEN
This paper describes the synthesis of fluorescent peptoids using the Ugi multicomponent reaction (4CR). The four synthesized structures had their photophysical properties evaluated and their potential as biomarkers established. The peptidomimetics were used at very low concentrations (10 nM) to follow their internalization in breast cancer cells and had their localization precisely determined. One of the new peptoids displayed mitochondrial affinity and stained this important organelle selectively. Co-staining experiments using MitoTracker Red confirmed the localization inside live cells.
Asunto(s)
Biomarcadores de Tumor/química , Colorantes Fluorescentes/química , Peptidomiméticos/química , Peptoides/química , Línea Celular Tumoral , Colorantes Fluorescentes/metabolismo , Humanos , Microscopía Fluorescente , Mitocondrias/química , Peptoides/síntesis químicaRESUMEN
In this article, we describe the synthesis of a small library of short peptoids composed of four glycine residues and acylated with a fatty acid that showed a remarkable in vitro activity against two fungal plant pathogens. Their straightforward synthesis implied two consecutive Ugi reactions and can be efficiently extended to the construction of highly diverse libraries.
Asunto(s)
Antifúngicos/síntesis química , Antifúngicos/farmacología , Fusarium/efectos de los fármacos , Peptoides/síntesis química , Peptoides/farmacología , Plantas/efectos de los fármacos , Plantas/microbiología , Acilación , Aminas/química , Antifúngicos/química , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Peptoides/química , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
A wide range of N-alkylglycines (peptoids) can be efficiently prepared via Ugi reactions using microwave irradiations. The results confirm the versatility and efficiency of the methodology for the preparation of functionalized peptoids. The products can be used in consecutive Ugi reactions to yield cyclic peptoids of potential biological interest.