RESUMEN
Owing to their structural diversity, peptides are a unique source of innovative active ingredients. However, their development has been challenging because of their disadvantageous pharmacokinetic (PK) properties. Over the past decade, many attempts have been made to improve the oral bioavailability of peptide drugs. In this review, we highlight the most recent and promising techniques aimed at the improvement of the oral bioavailability of peptides. The most recent findings will influence future approaches of pharmaceutical companies in the development of new, more efficient, and safer orally delivered peptides.
Asunto(s)
Administración Oral , Sistemas de Liberación de Medicamentos/métodos , Péptidos , Disponibilidad Biológica , Descubrimiento de Drogas/tendencias , Humanos , Péptidos/farmacocinética , Péptidos/uso terapéuticoAsunto(s)
Antiinflamatorios/química , Antineoplásicos/química , Neoplasias/tratamiento farmacológico , Pirazoles/química , Piridinas/química , Antiinflamatorios/síntesis química , Antiinflamatorios/uso terapéutico , Antineoplásicos/síntesis química , Antineoplásicos/uso terapéutico , Sitios de Unión , Línea Celular Tumoral , Simulación por Computador , Ciclooxigenasa 1/química , Ciclooxigenasa 1/metabolismo , Ciclooxigenasa 2/química , Ciclooxigenasa 2/metabolismo , Inhibidores de la Ciclooxigenasa 2/síntesis química , Inhibidores de la Ciclooxigenasa 2/química , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Inhibidores de la Ciclooxigenasa/síntesis química , Inhibidores de la Ciclooxigenasa/química , Inhibidores de la Ciclooxigenasa/uso terapéutico , Humanos , Pirazoles/síntesis química , Pirazoles/uso terapéutico , Piridinas/síntesis química , Piridinas/uso terapéuticoRESUMEN
New linear and cyclic guanidines were synthesized and tested in vitro for their antifungal activity toward clinically relevant strains of Candida species, in comparison to fluconazole. Macrocyclic compounds showed a minimum inhibitory concentration in the micromolar range and a biological activity profile in some cases better than that of fluconazole. One macrocyclic derivative was also tested against Aspergillus species and showed high antifungal activity comparable to that of amphotericin B and itraconazole.
