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From Biodiversity to Chemodiversity: Novel Plant Produced Compounds with Agrochemical and Cosmetic interest

Final Report Summary - AGROCOS (From Biodiversity to Chemodiversity: Novel Plant Produced Compounds with Agrochemical and Cosmetic interest)

Executive Summary:
The aim of the project was to discover and carry to the stage of development candidates; plant derived small molecules with potential as new cosmetic and agrochemical agents. These compounds have derived from plants originating from major biodiversity hotspots in Europe, Africa, Latin America, and the Asia-Pacific regions. The starting point of the project was a diversity-oriented natural product library of 484 compounds, from which promising scaffolds have been identified by a screening. Chemotaxonomy and chemodiversity oriented collection of plant material and 1810 plant species/organs, the generation of a library of 3620 extracts, and a state-of-the-art technology platform for miniaturized natural product discovery have been generated focused sub-libraries around these privileged scaffolds. A selection of 100 hit extracts was generated comprising of 60 active extracts with agrochemical properties and 40 active extracts with cosmetic potential. The hit extracts were microfractionated in order to focus the selected activity in active fractions, and the plant extracts were phytochemically investigated with state-of the-art techniques, for the isolation of the active constituents. All components (4000 microfractions and 100 isolated compounds) were examined for their biological properties: fungicidal, herbicidal, insecticidal (agrcochemicals) and antioxidant, UV-B protective and antityrosinase (cosmetics). All data resulting from the extensive bioevaluation, spectral characterization and profiling of the active extracts and compounds were incorporated in the Agrocos Database, implemented to foster this large number of data and provide solutions for easy dereplication of extracts. The evaluation of the existing results, in combination with advanced cellular biological evaluation and feasibility of commercialization, indicated five leads: three leads directed for cosmetic applications, and two leads for fungicidal agrochemical applications. A feasibility study was performed for the development of cosmetic agents from Greek biodiversity and several entries in the public media were published in order to communicate and support the important findings and the extent possibilities of development.
Project Context and Objectives:
The aim of the project was to discover and carry to the stage of development candidates, plant derived small molecules with potential as new cosmetic and agrochemical agents. These compounds have derived from plants originating from major biodiversity hotspots in Europe, Africa, Latin America, and the Asia- Pacific regions. The starting point of the project was a diversity-oriented natural product library of 484 compounds, from which promising scaffolds are identified by a screening. Chemotaxonomy and chemodiversity oriented collection of plant material, the generation of a library of 3620 extracts, and a state-of-the-art technology platform for miniaturized natural product discovery have generated focused sub-libraries around these privileged scaffolds. Further evaluation of these sub-libraries led to the development of novel products in agrochemistry and/or cosmetics with new or improved properties over existing active ingredients. Through this rationale based process, five leads resulted from Agrocos research, three extracts with cosmetic potential and two candidates for agrochemical development. A feasibility study was conducted for the potential development of an extract enriched in compounds possessing cosmetic properties (antioxidant, UV-B protective and skin whitening), stemming from the Greek flora. 
The results were successfully disseminated via contributions at scientific congresses, workshops, research and by releases to the non-scientific community via the press, internet, press releases, newsletters, and video sources.
Through Agrocos, key-concepts were addressed with the establishment of
• a structurally diverse small molecule natural product library encompassing pure compounds from plants of geographically distant and megadiverse regions, to serve as a quick entry to scaffolds of potential interest for the cosmetic and agricultural applications sought
• a focused library of plant extracts assembled on the basis of chemodiversity and chemotaxonomy considerations, originating from plants from hotspots of biodiversity and endemism, to provide sub-libraries of compounds around the shortlisted scaffolds
• efficiency and traceability due to a high degree of standardization, automation and miniaturization in the generation and management of libraries, screening, and in profiling thanks to the development of a common platform for management and use of sample related spectral data and metadata.
• use of relevant in vitro assays for major areas of use in cosmetics and as agrochemicals like fungicidal, herbicidal and insecticidal evaluation for agrochemical use, and antioxidant, UV-B protective and anti-tyrosinase evaluation for cosmetic use
• complementary expertise available at the different partners of the consortium
Key objectives of Agrocos included:
• Discovery and characterization of novel plant derived small molecule-type natural products which qualify as development candidates for new cosmetic and agrochemical agents with innovative or improved properties
• Establishment of screening libraries with an unprecedented level of library-related spectroscopic information and metadata
• Development of new concepts for integrating information contents with screening libraries
• Enhancing the competitiveness of European cosmetic and agrochemical industry through discovery of 
novel compounds for development
Opening new potentialities for the development of natural products derived from economically less 
favored but megadiverse regions, for sustainable production of products with high consumer acceptance


Project Results:
See attachment
Potential Impact:
Agrocos aims to produce European added value by
• enhancing the pan-European public awareness of biodiversity of natural resources
• expanding the biochemical diversity of natural product libraries, generating novel lead compounds of plant origin
• improving the competitiveness of the European and non-European industry
• improving the sustainability and eco-efficiency of these products
• proposing novel uses of the target plant species, whose economic role may have been so far very limited or non existent.
The diversity of activities carefully planned in AgroCos project have contributed to:
• Enhance the pan-European public awareness of biodiversity of natural resources. The first objective of the AgroCos project was the consolidation of an international cooperative network of scientific institutions and private industries of Europe, Latin America, Africa, and the Asian Pacific devoted to the discovery of new natural products with useful properties as cosmetic or agricultural agents. Agrocos’ research results have improved knowledge and public understanding of biodiversity, for managing biodiversity, and for developing novel products, processes and services derived from biodiversity. Through the dissemination activities e.g. organization of international workshop, web page construction, press releases to the mass media, scientific publications to specialized research journals and participation in international congresses our efforts have enhance the pan-European public awareness of biodiversity of natural resources. Major aims of those activities included: understanding, documenting and conserving plant diversity; depict pathways for the sustainable use of this diversity; promoting education and awareness about plant diversity; and strengthening conservation networks at both regional and national levels.

• Expand the biochemical diversity of natural product libraries, generating novel lead compounds of plant origin. The core activities of AgroCos aimed to take advantage of cutting edge technologies in Natural Products extraction, profiling and activity determination in order to generate a natural product library originating from taxonomically and geographically highly diverse plants, and the identification of a set of compounds with structurally diverse scaffolds. The designed methodology has facilitated dereplication problems, and enable us to the discovery of new molecular scaffolds of potential interest for the cosmetic and agricultural applications. Given that the plant samples originate from geographically distant megadiverse regions and have thus included mostly uninvestigated species, AgroCos has significantly expand the biochemical diversity of natural product libraries and generated novel lead compounds of plant origin. These efforts have taken us far beyond current state-of-the-art and have resulted in a unique, focused library of plant extracts assembled on the basis of chemodiversity and chemotaxonomy considerations.

• Improve the competitiveness of the European and non-European industry. AgroCos consortium focused its activities in these two areas of application (agrochemicals and cosmetics) to develop new knowledge concerning underexploited plant species and select new compounds with improved properties (potency, selectivity, physico-chemical characteristics) for cosmetic and agrochemical applications. The EU market is the biggest cosmetics market in the world. With an average growth of 3.8% annually between 2005 and 2007, the EU27 market amounted to € 67.8 billion in 2007, according to Colipa, the European Cosmetics, Toiletries and Perfumery Association.
The natural cosmetics market is relatively small, but is growing faster than the overall market. Natural cosmetics continued to benefit from growing health concerns, a sense of well-being and looking good, as well as the influence of media attention. Within this overall picture, there is an increasing use of new, active natural ingredients with functional benefits, organic ingredients, exotic, African and Amazon ingredients and ingredients (saps and extracts, essential oils and vegetable oils) based on (exotic) fruits. On the other hand the increasing consumption of organic foods has created a pressing need for natural insecticides and herbicides that can be used on crops certified as "organic". Ideally, insecticides should reduce pest populations, be target-specific (kill the pest but not other organisms), break down quickly, and have low toxicity to humans and other mammals. As a result, there is increasing demand for alternatives to conventional synthetic insecticides. Many botanical insecticides have been known and used for hundreds of years, but were displaced from the marketplace by synthetic insecticides in the 1950s. Thee figures show that there is considerable market potential for future natural product-based agrochemical and personal care products. Hence, the economic impact for the European industry launching new commercial products based on natural sources will be accordingly. The exploitation of new plant-derived products will have significant economic impact in the source countries. AgroCos project is committed to an efficient study and testing of natural products as well as the development in scientific and technological capacity increasing thus access to new species and development of new commercial research. Moreover through the implementation of the project closer relationships with source countries and communities will build up in the future which allow the design of benefit-sharing packages to link not only the supply of raw material, but also local capacity- and institution-building.

• Improving sustainability and eco-efficiency of natural products. Through the AgroCos project activities possibilities for the utilization of natural resources in cosmetology and agriculture have been assessed and strategies for conservation and sustainable supply have been investigated. We believe that from the plant species that were studied it is possible to identify endemic plants that are viable economic opportunities for farmers as high value alternative crops giving new opportunities for environmentally friendly sustainable development. These issues have been thoroughly considered in the feasibility study which has been carried out within the activities of WP5. The possibility of cultivation in the different regions represented in the AgroCos consortium has been partially examined in order to investigate the sustainability and eco-efficiency of the products that will be considered for future development. Moreover the development of environmental friendly industrial procedures within this project have give the opportunity to herbal extract and flavour producer to adopt technologies in line with EU policies for the protection of environment.

List of Websites:
http://www.agrocos.eu/
final1-final-report-agrocos-.pdf