International Cooperative Biodiversity Group Program Research Articles

Portobelamides A and B and Caciqueamide, Cytotoxic Peptidic Natural Products from a Caldora sp. Marine Cyanobacterium.

Three new compounds, portobelamides A and B (1 and 2), 3-amino-2-methyl-7-octynoic acid (AMOYA) and hydroxyisovaleric acid (Hiva) containing cyclic depsipeptides, and one long chain lipopeptide caciqueamide (3), were isolated from a field-collection of a Caldora sp. marine cyanobacterium obtained from Panama as part of the Panama International Cooperative Biodiversity Group Program. Their planar structures were elucidated through analysis of 2D NMR and MS data, especially high resolution (HR) MS2/MS3 fragmentation methods. The absolute configurations of compounds 1 and 2 were deduced by traditional hydrolysis, derivative formation, and chromatographic analyses compared with standards. Portobelamide A (1) showed good cytotoxicity against H-460 human lung cancer cells (33% survival at 0.9 μM).

To discover bioactive compounds from the plants in Lingnan region of Southern Asia

Lingnan is a geographic region referring to “Five Ranges”, which covers five Southern provinces of China and northern part of Vietnam. It is located in a tropical and sub-tropical climate zone with rich rainforests and diversified plant resources. For a decade, our research programs have investigated the chemical and biological properties of several thousands of the terrestrial plant samples in Lingnan region. We have evaluated the plant samples against cancer, parasites, fungi, bacteria and viruses (Figure 1). Bioassay-guided fractionation of the selected plant extracts led to the isolation of more than 300 compounds of varying degrees of structural complexity, novelty and/or biological activity (anticancer, antiviral, anti-bacterial, anti-fungal and antimalarial activities). [The work described in this paper was collaborative efforts within multi-disciplinary cooperative programs supported by grants from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. HKBU 262912 and HKBU12103014), HKBU Interdisciplinary Research Matching Scheme (RC-IRMS/12 – 13/03), Faculty Research Grants, Hong Kong Baptist University (FRG2/14 – 15/047 and FRG1/13 – 14/029), and NIH Grants 3U01TW001015 – 10S1 and 2U01TW001015 – 11A1 (administered by the Fogarty International Center as part of an International Cooperative Biodiversity Groups program, through funds from NIH, NSF, and Foreign Agricultural Service of the USDA)].

Four antimalarial limonoids isolated from Carapa guianensis and two antiproliferative diterpenes isolated from Hypoestes SP.

In a search for antimalarial natural products from plants in collaboration with the Natural Products Discovery Institute we investigated an antiplasmodial extract from Carapa guianensis (Meliaceae). This extract gave a DCM fraction with activity against the chloroquine-resistant Dd2 strain of P. falciparum with an IC50 value about 4 µg/mL. The four active limonoids (1 – 4) were isolated from this fraction and their structures were elucidated by 1D and 2D NMR spectroscopic and MS data. This is the first report of the antimalarial activity of 6α,11β-diacetoxygedunin (1). In a separate study as part of our work in the Madagascar International Cooperative Biodiversity Group program, two diterpenes with good antiproliferative activity against the A2780 human ovarian cancer cell line as well as antimalarial activity were found in the hexanes fraction from the extract of Hypoestes sp. (Acanthaceae). This is the first report of the activity of crotonolide G (5) towards A2780 cell lines and of its antiplasmodial activity.

Natural Products Discovery at the Missouri Botanical Garden: Supporting Discovery Programs with Botany, Ethnobotany and Conservation

The Missouri Botanical Garden has participated in several major domestic and international natural products discovery programs. Involvement of botanists in land plant collections is necessary for sample identification, and ethnobotanical data may inform collection strategies or provide additional perspectives on research results. In addition, conservation-related work can contribute materially to developing-country collection programs both by preserving natural vegetation for future access and by providing a return of benefits to local communities, which is ethically and often legally required. MBG's participation in the International Cooperative Biodiversity Group program in Madagascar serves as a useful example. Results of antimalarial assays performed by the Centre National d'Application des Recherches Pharmaceutiques, a participating Malagasy research institution, can be compared to ethnobotanical data. MBG's onsite conservation facilitators work with communities near collection sites to set up conservation and sustainable development programs designed to respond to local needs and preferences. Those projects are not only responsible for the creation of new protected areas and land-use rules, but for meaningful improvements in local communities' welfare, which, among other things, increases the likelihood that future collections will be permitted.

The impact of the United Nations Convention on Biological Diversity on natural products research

The discovery and development of novel, biologically active agents from natural sources, whether they be drugs, agrochemicals or other bioactive entities, involve a high level of interdisciplinary as well as international collaboration. Such collaboration, particularly at the international level, requires the careful negotiation of collaborative agreements protecting the rights of all parties, with special attention being paid to the rights of host (source) country governments, communities and scientific organizations. While many biodiversity-rich source countries currently might not have the necessary resources for in-country drug discovery and advanced development, they provide valuable opportunities for collaboration in this endeavor with research organizations from more high-income nations. This chapter discusses the experiences of the US National Cancer Institute and the US government-sponsored International Cooperative Biodiversity Groups program in the establishment of international agreements in the context of the Convention of Biological Diversity's objectives of promoting fair and equitable collaboration with multiple parties in many countries, and includes some specific lessons of value in developing such collaborations.

Using Licensing Contracts to Protect Holders of Traditional Knowledge Related to Genetic Resources: A Reflection on ICBG Projects

During recent decades, role of traditional knowledge (TK) in biotechnology development has become increasingly important. The benefits resulting from TK exploration can be tremendous. Due its significant economic and healthcare contribution society, owners of TK (local and indigenous communities) should be sufficiently compensated for use of their knowledge and their rights on TK should also be properly protected. Contracts are considered be one of major means ensure fair benefit-sharing based on mutually agreed terms between TK users and holders. Contractual agreements are not novel in transactions involving access genetic resources and benefit sharing. The most famous and earliest case was Merc-INBio agreement. TK has always been only part of such agreements - usually mentioned under prior informed consent - or else it has simply been omitted. Indigenous peoples (or their representatives) have seldom become a party such contracts. Still, history of TK exploration revealed several more or less successful cases, where TK holders acted as rightful parties associated transfer of genetic resources. The International Cooperative Biodiversity Group (ICBG) Program was established in 1992 by National Institute of Health (NIH), National Science Foundation (NSF) and U.S. Agency for International Development (later replaced by Department of Agriculture (USDA)) run multidisciplinary projects addressing drug devlopment, biodiversity conservatio and economic growth. More than a dozen projects in 18 countries in Aisa, Africa and Latin America have been supported under Program. Seven International Cooperative Biodiversity Groups (awards) are currently being financed. The source of funding in ICBG projects can be from both public and private sectors. Another essential goal of Porgrams is to develop models for sustainable and equitable commercial use of biodiversity-rich ecosystems. According collaboration agreement, bioprospectors obtain access biological material (including genetic resources) and are required share benefits derived from use of these resources and associated TK with biosuppliers and TK holders. A critical point of ICBG Program is the development of ethically sound partnerships among diverse collaboration agreement is verified comply with principles of prior informed consent (PIC), access and benefir-sharing (ABS) and a number of intellectual property rights issues. Each project under ICBG is a kind of bridge or a collaborating forum that brings together interested parties for formulation of an agreement and provides a mechanism for negotiations. The ICBG Program ensres a relatively integrated and successful international licensing scheme of collaboration between indigenous communities, research institutions and private entities (U.S., international or multinational), which assists development of creative potential solutions for anti-biopiracy and efficient exploitation and sustainable use of biological resources and associated TK. An ICBG project usually involves a multinational pharmaceutical coporation, a nongovernmental organization, a reseach university and collaborating partners from source country (research institute, indigenous communities or their representatives). ICBG projects are characterized by direct involvement of TK holders, or their legal representatives in contractual agreement as rightful parties. Prior infromed consent and associated measures are a mandatory part of all ICBG projects. Nevertheless, this article points out difficulties TK holders and their representative may envounter and how they can overcome limitations in a contractual arrangement, such as an imbalance of bargaining power and difficulties in enforcement. In following section, we will address general structure and main features of ICBG progects. In second part of this article, we will discuss three contractual agreements of ICBG projects, including Peru-ICBG, Maya-ICBG and UIC-Vietnam-Laos-ICBG, and address their mechanisms of TK protection. In third part, we will summarize thes three programs. In fourth part, we will discuss advantages and flaws of contractual arrangement with regard TK protection. Finally, we will present our suggestions and solutions.

Cytotoxic Veraguamides, Alkynyl Bromide-Containing Cyclic Depsipeptides from the Marine Cyanobacterium cf. Oscillatoria margaritifera

A family of cancer cell cytotoxic cyclodepsipeptides, veraguamides A-C (1-3) and H-L (4-8), were isolated from a collection of cf. Oscillatoria margaritifera obtained from the Coiba National Park, Panama, as part of the Panama International Cooperative Biodiversity Group program. The planar structure of veraguamide A (1) was deduced by 2D NMR spectroscopy and mass spectrometry, whereas the structures of 2-8 were mainly determined by a combination of 1H NMR and MS2/MS3 techniques. These new compounds are analogous to the mollusk-derived kulomo'opunalide natural products, with two of the veraguamides (C and H) containing the same terminal alkyne moiety. However, four veraguamides, A, B, K, and L, also feature an alkynyl bromide, a functionality that has been previously observed in only one other marine natural product, jamaicamide A. Veraguamide A showed potent cytotoxicity to the H-460 human lung cancer cell line (LD50=141 nM).

Plant-based research among the International Cooperative Biodiversity Groups

The International Cooperative Biodiversity Groups (ICBG), administered by the Fogarty International Center, was created in 1992. By 2007, the program had completed three cycles of funding. In the last cycle (2003-2008), seven ICBGs were operating in biodiversity hotspots around the world with support from nine Institutes and Centers of the National Institutes of Health and from the National Science Foundation and the US Department of Agriculture. Accomplishments over the history of the program include discovery of numerous bioactive compounds, training of thousands of young scientists in the US and abroad, and the creation and enhancement of biodiversity protected areas around the world. Over the history of the ICBG program plant-based research has been a significant component of many projects. Over 10,000 species of tropical, temperate and arid lands plants from 350 plant families have been analyzed. While some of the research has been guided by ethnobotanical science, particularly science oriented toward botanical medicines, much has been focused around diversity-oriented collections, and some have used ecological principles to identify active compounds. While marine and microbial organisms have grown in importance among the natural products research community, plants will continue to play important roles for the foreseeable future.

The UIC ICBG (University of Illinois at Chicago International Cooperative Biodiversity Group) Memorandum of Agreement: a model of benefit-sharing arrangement in natural products drug discovery and development.

The Convention on Biodiversity mandates a new approach to the discovery of natural product drugs, one that incorporates concepts of national ownership of genetic resources, intellectual property rights in traditional knowledge, and sharing of economic benefits with countries that are the source of new natural products. The International Cooperative Biodiversity Group (ICBG) program was established to support experimentation in implementation of the Convention through development and execution of international agreements for bioprospecting. The agreement of one such ICBG program, between the University of Illinois at Chicago and institutions in Vietnam and Laos, is presented here. The core elements contained in the single, five-way Memorandum of Agreement are the arrangements for intellectual property rights, treatment of informed consent, and plans for benefit-sharing (including the sharing of short- and long-term royalty benefits, capacity building, and community reciprocity). Program participants were able to develop a practical and flexible agreement that satisfies the wishes of all institutions that are parties to it.