ABSTRACT
The classical approach to drug discovery from natural products (NP's) requires strenuous and complex purification steps for the isolation and structural elucidation. Modern strategies as dereplication aim to accelerate the identification of known compounds present in a crude or partially purified extract. In this work, we investigated the influence of the solid-phase extraction (Oasis, Plexa, and Agilent C18 cartridges with and without organic modifiers) chemical profile obtained by UPLC-QTOF-MS and NMR and cytotoxicities of aqueous extracts from Phyllanthus niruri and P. amarus. Our results showed differences between the SPE cartridges and the mass recovered. P. niruri showed higher mass recovery than P. amarus indicating a higher amount of secondary metabolites. The UPLC-QTOF-MS analysis revealed that P. niruri crude extract presents higher contents of phenolic compounds than P. amarus. According to NMR analysis, P. niruri contained more tyrosine, corilagin, and glycosidic residues while P. amarus, presented higher content of ellagic acid. The different stationary phases, as well as mobile phases for exploratory SPE, enabled the exploitation of the different chemical functionalities within the Phyllanthus species. The SPE (MeOH:H2O 70:30 with C18 cartridges) samples showed greater in vitro cytotoxicity than the crude extracts, with IC50 ranging from 8.01 to 94.92⯵gâ¯mL-1 against the tumor lines tested. The solid phase extraction allowed the concentration of molecules with desirable physicochemical characteristics, which might increase the hit of therapeutically useful substances.
Subject(s)
Cell Survival/drug effects , Chromatography, High Pressure Liquid/methods , Phyllanthus/chemistry , Plant Extracts/pharmacology , Solid Phase Extraction/methods , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Discovery , Humans , Magnetic Resonance Spectroscopy/methods , Mass Spectrometry/methods , Plant Extracts/chemistry , Plant Leaves/chemistryABSTRACT
Environmental exposure to genotoxic agents represents a major health concern for modern society. DNA damage could lead to mutations, which accumulative effect is closely related to degenerative and lethal diseases, such as cancer. Because of their structural and chemical diversity natural products play a fundamental role in pharmaceutical sciences for novel drug discovery. The present review article focuses on pre-clinical studies done with some species from Cuban flora that have been tested with positive antigenotoxic properties against different genotoxins. Special emphasis regarding molecular mechanisms suggested, from antioxidant activity to DNA repair modulation, a critical discussion of the state of art and the perspectives in the use of these plants as a new and promising strategy for genoprotection in the 21st Century are included.
La exposicioÌn ambiental a agentes genotoÌxicos representa un problema de salud significativo en la sociedad actual. El danÌo al ADN puede generar mutaciones, cuyo efecto acumulativo se encuentra estrechamente relacionado con enfermedades degenerativas y letales como el caÌncer. Debido a su diversidad estructural y quiÌmica los productos naturales juegan un papel fundamental en las ciencias farmaceÌuticas en el descubrimiento de nuevas drogas. El presente artiÌculo de revisioÌn puntualiza estudios pre-cliÌnicos realizados con determinadas especies de la flora cubana que han sido estudiadas con una respuesta antioxidante positiva frente a diferentes genotoxinas. Se enfatizan especialmente los mecanismos moleculares sugeridos, desde actividad antioxidante hasta modulacioÌn de la reparacioÌn del ADN, asiÌ como una discusioÌn criÌtica del estado del arte y las perspectivas en el empleo de estas plantas como una estrategia nueva y prometedora para la genoproteccioÌn en el siglo 21.