Feature-Based Molecular Network-Guided Dereplication of Natural Bioactive Products from Leaves of Stryphnodendron pulcherrimum (Willd.) Hochr.

Stryphnodendron pulcherrimum is a species known to have a high content of tannins. Accordingly, its preparations are used in southern Pará, Brazil, for their anti-inflammatory and antimicrobial activities, but so far, its chemical profile composition remains essentially unknown. We herein describe the compounds present in a hydro-acetonic extract from S. pulcherrimum leaves as revealed by dereplication via ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry. The data were combined with spectral organization, spectral matching through the Global Natural Products Social platform, in silico annotation and taxonomical ponderation. Several types of phenolic compounds were identified such as gallic acids, flavan-3-ols and flavone-like compounds. From these, 5 have been recently reported by our group, whereas 44 are reported here for the first time in this tree species, and 41 (out of 49) for this genus. The results highlight the possible role of Stryphnodendron pulcherrimum as a renewable source for natural bioactive products with potential pharmaceutical applications.

Secure and Sustainable Sourcing of Plant Tissues for the Exhaustive Exploration of Their Chemodiversity.

The main challenge of plant chemical diversity exploration is how to develop tools to study exhaustively plant tissues. Their sustainable sourcing is a limitation as bioguided strategies and dereplication need quite large amounts of plant material. We examine if alternative solutions could overcome these difficulties by obtaining a secure, sustainable, and scalable source of tissues able to biosynthesize an array of metabolites. As this approach would be as independent of the botanical origin as possible, we chose eight plant species from different families. We applied a four steps culture establishment procedure, monitoring targeted compounds through mass spectrometry-based analytical methods. We also characterized the capacities of leaf explants in culture to produce diverse secondary metabolites. In vitro cultures were successfully established for six species with leaf explants still producing a diversity of compounds after the culture establishment procedure. Furthermore, explants from leaves of axenic plantlets were also analyzed. The detection of marker compounds was confirmed after six days in culture for all tested species. Our results show that the first stage of this approach aiming at easing exploration of plant chemodiversity was completed, and leaf tissues could offer an interesting alternative providing a constant source of natural compounds.

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.