Innovative Strategies in the Search for Bioactive Plant Constituents

Abstract

AbstractHigher plants represent a rich source of new molecules with interesting pharmacological properties that could be used as lead compounds for the development of new drugs. During the past decade, the investigation of the secondary metabolites from plants has led to the introduction of several important new drugs, such as apomorphine (Apokyn®) for the treatment of Parkinson's disease, nitisinone (Orphadin®) for the treatment of hereditary tyrosinaemia type 1, and miglustat (Zavesca®) for the treatment of the Gaucher disease. Success in drug discovery research using plants is dependent on various issues, but plant selection remains key for all types of these studies. The choice of the appropriate plant material is usually based on information from traditional medicine, chemotaxonomic data, field observation, or random collection. Recently, other approaches have been used, such as reverse pharmacognosy induction of new compounds by stress induction or biotransformation. Extraction and enrichment procedures are also key to avoid chemical degradation and detect the active constituents among hundreds of nonactive constituents before submitting the sample for a first biological screening. New high throughput screening (HTS) strategies have been used to rapidly and efficiently evaluate the biological and chemical potentials of complex matrices, such as plant extracts. In this field, the creation of enriched extracts of natural product (NP) fraction libraries, notably using automatic procedures, opens new possibilities for the research of new lead compounds from higher plants. On the other hand, tremendous advances have been made in molecular biology, affording the development of more predictablein vitroandin vivobioassays. The combination of metabolite profiling and bioassays that can directly be performed on the fractions that are resolved by analytical high performance liquid chromatography (HPLC) provides the possibility of distinguishing between already‐known bioactive compounds and new molecules directly isolated from crude plant extracts (dereplication). Thus, the tedious isolation of compounds of low interest can be avoided and a targeted isolation of new bioactive products or constituents presenting novel or unusual spectroscopic features can be undertaken. The applications, possibilities, and limitations of the latest technologies applied to the study of plant metabolites, as well as future developments expected in this field, are discussed.