Unraveling Plant Natural Chemical Diversity for Drug Discovery Purposes

The screening and testing of extracts against a variety of pharmacological targets in order to benefit from the immense natural chemical diversity is a concern in many laboratories worldwide. And several successes have been recorded in finding new actives in natural products, some of which have become new drugs or new sources of inspiration for drugs. But in view of the vast amount of research on the subject, it is surprising that not more drug candidates were found. In our view, it is fundamental to reflect upon the approaches of such drug discovery programs and the technical processes that are used, along with their inherent difficulties and biases. Based on an extensive survey of recent publications, we discuss the origin and the variety of natural chemical diversity as well as the strategies to having the potential to embrace this diversity. It seemed to us that some of the difficulties of the area could be related with the technical approaches that are used, so the present review begins with synthetizing some of the more used discovery strategies, exemplifying some key points, in order to address some of their limitations. It appears that one of the challenges of natural product-based drug discovery programs should be an easier access to renewable sources of plant-derived products. Maximizing the use of the data together with the exploration of chemical diversity while working on reasonable supply of natural product-based entities could be a way to answer this challenge. We suggested alternative ways to access and explore part of this chemical diversity with in vitro cultures. We also reinforced how important it was organizing and making available this worldwide knowledge in an “inventory” of natural products and their sources. And finally, we focused on strategies based on synthetic biology and syntheses that allow reaching industrial scale supply. Approaches based on the opportunities lying in untapped natural plant chemical diversity are also considered

Les produits de l'anacardier : caractéristiques, voies de valorisation et marchés

Originaire du Brésil, l'anacardier est largement présent dans la zone intertropicale. Une synthèse sur les intérêts économiques et les différentes voies de valorisations des produits de cet arbre a été effectuée. De part sa résistance, notamment aux périodes de sécheresse, l'espèce Anacardium occidentale (anacardiacée) est adaptée à de nombreuses zones tropicales. Malgré sa tolérance aux attaques parasitaires, elle peut être sensible à certains insectes et attaques fongiques comme l'oïdium. Les rendements moyens obtenus pour la noix sont d'environ 600 kg x ha -1 x an-1; ils sont susceptibles d'être améliorés grâce à la sélection variétale. La noix de cajou est le fruit de l'anacardier au sens botanique du terme. L'amande est riche en lipides et contient environ 20% de protéines. En 1999, les principaux producteurs mondiaux de noix de cajou ont été l'Inde, le Nigéria, le Brésil et la Tanzanie, qui ont produit chacun plus de 100 000 t x an-1. Après concassage de la coque et émondage, ce produit à forte valeur ajoutée est le plus souvent exporté. La pomme de cajou correspond au pédoncule hypertrophié de la noix qui possède à maturité une chair juteuse et sucrée. Ses principales caractéristiques sont son astringence et sa teneur élevée en vitamine C (200-300 mg x 100 g-1). La pomme de cajou est assez peu valorisée sauf en Inde et au Brésil, notamment sous forme de jus de fruit. Le baume de cajou est une production secondaire assez originale : extrait des coques de la noix, ce liquide corrosif, riche en composés phénoliques, est utilisé dans l'industrie chimique. La culture de l'anacardier, avec sa diversité de produits et notamment avec la noix qui est bien intégrée aux marchés internationaux, semble pouvoir constituer une source intéressante de revenus pour les zones tropicales sèches. Néanmoins, la pomme mériterait d'être mieux valorisée car elle reste encore un sous-produit de l'industrie de la noix de cajou. (Résumé d'auteur

Fast method for the simultaneous quantification of toxic polyphenols applied to the selection of genotypes of yam bean (Pachyrhizus sp.) seeds.

The purpose of the research was to develop and validate a rapid quantification method able to screen many samples of yam bean seeds to determine the content of two toxic polyphenols, namely pachyrrhizine and rotenone. The analytical procedure described is based on the use of an internal standard (dihydrorotenone) and is divided in three steps: microwave assisted extraction, purification by solid phase extraction and assay by ultra high performance liquid chromatography (UHPLC). Each step was included in the validation protocol and the accuracy profiles methodology was used to fully validate the method. The method was fully validated between 0.25mg and 5mg pachyrrhizin per gram of seeds and between 0.58mg/g and 4mg/g for rotenone. More than one hundred samples from different accessions, locations of growth and harvest dates were screened. Pachyrrhizine concentrations ranged from 3.29mg/g to lower than 0.25mg/g while rotenone concentrations ranged from 3.53mg/g to lower than 0.58mg/g. This screening along with principal component analysis (PCA) and discriminant analysis (DA) analyses allowed the selection of the more interesting genotypes in terms of low concentrations of these two toxic polyphenols