Quim. Nova, Vol. 24, No. 1, 153-155, 2001.

Assuntos Gerais

MEDICINAL CHEMISTRY IN THE DEVELOPMENT OF SOCIETIES.

IUPAC Comission of Medicinal Chemistry*

Recebido em 7/11/00

This document here has been elaborated by the IUPAC Medicinal Chemistry section and is backed by
a large number of scientists, many of whom have had direct involvement and whose names appear at
the end of the article. This work discusses the role that the discovery of new medicinal agents has in
the development of societies as well as in the conservation of biodiversity in terms of the work carried
out on natural products. Also included are several recommendations for countries which are presently
in search of their own scientific and technological development in medicinal agents. The IUPAC
Medicinal Chemistry section would appreciate the collaboration of the scientific societies in every
country to aid in the diffusion of this document.

Keywords: medicinal chemistry; biodiversity; development of societies.

Modern times have seen globalization of all human biodiversity is attributable to chemical constituents of plants with
endeavors accompanied by a seamless, sans frontiers, diffusion an array of complex structures, many of which have not yet
of culture, ideas and science across traditional boundaries of succumbed to total, practical syntheses by man. To lose
territories, cultures and societies. However, all societies are biodiversity is to lose information of great potential value.
not at the same level of development and a significant This article intends to refine and further promote ideas
challenge still lies in respecting and harnessing our differences proposed during earlier projects of the IUPAC Medicinal
to insure peace, justice and liberty for all. Chemistry section1-3. Specifically, the authors seek to enhance
For example, within the context of the life sciences a man- the transfer of science and technology associated with drug
made medicinal agent should receive special, international discovery and development between developed and developing
attention. Any compound that can help restore lost health or societies in the most mutually beneficial scenarios possible.
prevent a disease should be made available to all countries,
regardless of the continental location or the degree of societal INVERTING THE MODEL
development. The only limits that should exist are those which
are organizational, linked to preparation, distribution, etc. Irrespective of administrative or political considerations,
Presently there are countries which are the discoverers of companies and centers having high levels of development need
medicinal agents and there are countries which are simply to be brought together with those which lack it by means of
consumers. Likewise, there are countries whose legislation joint projects within the broad field of chemistry and,
pertaining to intellectual property rights are quite sophisticated especially, within the distinct area of biologically active
while there are others who do not have this type of legislation compounds. Various modes of interaction can be proposed:
at all. Some countries are in search of development with an the most often used is one wherein samples of materials from
overabundance of natural resources and biodiversity while others developing countries with biodiversity are extracted and
have the potential for scientific and technological exploitation transported for study in developed societies. We make a case
but lack such resources. In this wide panorama, the field of for an inversion of this traditional model, namely that of
chemistry can play an important role since medicinal agents are offering technology to the countries with biodiversity so that
chemical products which, in many cases, are often modified if they themselves may carry out the necessary developmental
not entirely prepared by chemical reactions. Likewise, work. Chemical research conducted in the country where
samples originate would enhance the country’s scientific deve-
lopment. Competitive capacity, research methodology and the
infrastructure could be the focus of negotiation and agreement.
* Authors: A. Monge - Centro de Investigación en Farmacobiología
The contributions to chemical research on bioactive molecules
Aplicada, Universidad de Navarra, Apdo. 177, 31080, Pamplona,
España; M. Chorghade - Chorghade Enterprises, 14 Carlson Circle, that biodiversity-rich, developing countries may be able to then
Natick, MA, 01760-4205, USA.; P. W. Erhardt - Ctr. for Drug return can be ascertained on the basis of:
Design & Development, Univ. Toledo, College of Pharmacy, 2801 Ø Strengths:
W. Bancroft Street, Toledo, OH, 43606-3390. US; C. R. Ganellin - • Biological material, both of animal and vegetable origin,
University College London, Department of Chemistry, Christopher with demonstrated or potential activity.
Ingold Laboratories, 20, Gordon Street, London, WC1H OAJ, UK.; • Traditional knowledge concerning biological activities,
N. Koga - Daiichi Pharmaceutical Co. Ltd., 14-10, Nihonbashi 3-
chome, Chuo-ku, Tokyo, 103-8234, Japan; P. Lindberg - Astra
linked to plants or animals.
Hässle AB. S-431 83. Mölndal, Sweden; T. J. Perun - Route 4. Ø Weaknesses:
Box 24. Hempstead. TX, 77445. USA.; J. G. Topliss - Department • Infrastructure deficiencies which cause difficulties for
of Medicinal Chemistry, University of Michigan, College of conducting scientific research.
Pharmacy, 428, Church Street, Ann Arbor, MI, 48109-1065, USA;
B. K. Trivedi – Parke-Davis Pharmaceutical Research, 2800 Importantly, the salient features of such programs should
Plymouth Road, Ann Arbor, MI 48105, USA; C. G. Wermuth - provide for: conservation of biodiversity; equitable intellectual
Université Louis Pasteur Strasbourg, Faculté de Pharmacie, 74, Route property rights/duties; and, development of scientific resources/
du Rhin, BP 24, F-67401, Illkirch Cedex, France. facilities/infrastructure.
154 Monge et al. Quim. Nova

MEDICINAL CHEMISTRY AND BIODIVERSITY Establishing ownership may not be simple. It is imperative
to begin by defining the discoverer7. In the discovery of medi-
Realizing that biodiversity can be lost by man-made cinal agents, by traditional ways of Medicinal Chemistry, this
cataclysms such as the construction of large public works or by can correspond to an individual researcher or to an entire
natural catastrophes such as fires, volcanoes etc., Medicinal research team. In plants with therapeutic applications originating
Chemistry can function as a great ally by emphasizing the eco- from native communities, the question is much more
balance between life and its surroundings, plants and micro- complicated. Here we are speaking more of a “chain” of
fauna and other relationships. Medicinal Chemistry also inventors. This can result in problems when it comes to the
recognizes the symbiotic interaction between native communities selection of the beneficiaries and the distribution of the benefits
and cultures as a foundation and wellspring for potential obtained. A matter of equal importance is the fact that certain
discoveries. These interrelationships must be nurtured and their cultures hold nature to be sacred and look askance at any
key elements preserved. Researchers studying natural medicinal attempts at its legal protection as a prelude to commercialization.
agents subscribe to this rationale. Their analysis, evaluation and Whether the traditional use of a plant for a given pathology
effective utilization of available resources can greatly assist constitutes public property and prior art is a vexing question.
toward maintaining the elements of biodiversity while promoting The protection of knowledge, within the context of plants with
scientific advances. Alternatively, in developing countries whose biological activity, cannot be easily accomplished via patents
economies are based on the exploitation of agricultural and and it becomes necessary to search for further avenues. From
livestock resources principally geared to the production of cash the standpoint of equity, answers may be able to be found during
crops and immediate products, there is great pressure on their the transfer of knowledge. Consider that the number of plants
natural space. Consequently, there is also great pressure toward which are presently used in their original form in therapeutics is
the potential elimination of their natural flora. Thus, the quite limited. In practice it is the process of bio-directed
relationships between biodiversity, opportunity and the fractionation of plant extracts that eventually permits us to find
structuring of various alliances become especially important compounds which then typically also undergo further structural
relative to the immediate financial needs of a developing country. modification to ultimately provide preferred molecules that are
In this light, however, biodiversity and Medicinal Chemistry more active and less toxic. Consequently, in this type of scenario
must find a way to collaborate and optimize opportunities based a patent covering the initial plant material may not be adequate.
on new alliances and technology transfer that is not based-upon The solution to this scenario of “plant-development” can lead
pure economics. Enormous benefits can accrue in the fields of to an impasse precisely for the countries in search of develop-
education, scientific research, and innovation when an ment, thereby possibly losing by default the possibilities for the
approach, other than immediate financial gain is taken. use of their biodiversity.
Some examples can be illustrative. The “uña de gato,” Economic compensation for historical knowledge should not
Uncaria tomentosa, DC, is a liana which has long been used by be lost during the overall development process because the living
native communities of South America. However, the people from materials may have needed protection and conservation, sometimes
the countries where the plant grows became wary of exporting throughout centuries, in order to ultimately afford the current
extracts for Medicinal Chemistry research because they thought validation of their use. This effort might be compensated for
they might not receive commensurate benefits. Ultimately the through a contract, establishing royalties that could be obtained
plant became offered on the net, in any quantity anywhere in when commercialization takes place. In line with our previous
the world by a few financially opportunistic companies. The discussion, the contract might also specify in advance of
result is that the opportunity toward incorporating technology commercialization and as part of a collaborative development
and technological development for the countries that originally venture, the training of persons and the acquisition of equipment
possessed the plant has been lost. Alternatively, the and technologies as well as the more typical payment for samples.
domestication of plants, such as the Catharanthus roseus G. For example, compensation could be provided to the persons that
Don of great interest in the production of anti-cancer alkaloids provide the plant, make the extracts, and carry out biological
like vincristine, represents a form of conservation of biodiversity, assays, in such a way that each one can maintain his or her own
of training in agricultural techniques of economic interest, and interest and ultimate stake in commercialization. The country
of the creation of a local chemical industry. obtains benefits directly through taxation corresponding to the
activities, and more importantly, through the scientific and
MEDICINAL CHEMISTRY AND OWNERSHIP OF technological upgrading of its society. The possibility of regional
NATURAL RESOURCES subsidiary or local companies playing a more important role in
the transference of research and technology in such collaborative
Recognizing the sovereign rights that each country has over scenarios should also be seriously considered.
its resources4, the aim of this report is to prompt compromises In countries with emerging economies, biodiversity and
between developed countries and developing countries in the related activities constitute “green gold.” For this reason, at
area of ownership. New circumstances 5 have emerged that times, the governments assume quick, financially-driven poli-
suggest reform of the traditional system of patents essential cies that can sometimes be contrary to eco-relationships. Thus,
for commercialization and diffusion of science. Presently, when both parties must be prepared to adopt longer-range planning
a native community produces a unique cloth, it can be copied considerations into their decision-making processes. Equity and
by the whole world because it is not legally protected. equal opportunity must be given to protect the discoveries
Alternatively, when an entity in a developed country copies made by any society. This principle of equity can ameliorate
and registers modifications based on the designs of a native any misunderstanding arising out of the actions of medicinal
community, absolutely no one, not even the original artists, chemists in developed countries in their relationship with their
can legally copy them6. It could be argued that the native counterparts in developing countries.
community has the sole responsibility to register its work in
order to obtain legal protection. However, such countries are SUMMARIAL POINTS
typically unable to do this because of a lack of knowledge
regarding these types of procedures or due to a scarcity of the Ø Medicinal Chemistry research on extracts from plants and
means to achieve such ends. The same situation can happen other living organisms that leads to the discovery of
with a galenic preparation of a plant that has biological activity therapeutic agents, can also be an important factor toward
when initially used by a traditional culture. maintaining biodiversity.
Vol. 24, No. 1 Medicinal Chemistry in the Development of Societies. Biodiversity and Natural Products 155

Ø Relationships between societies which possess important Facultad de Ciencias Experimentales. Urb. Montepríncipe. Ctra.
biodiversity and developed societies which possess Boadilla del Monte, 5,300. 28668 Madrid. SPAIN.
advanced technological processes should be based on the (RIIDDMED - CYTED).
principles of equity. They should operate by means of Ferrándiz García, Francisco. Vocal Asesor de Rel.
collaborative contracts which acknowledge progression of Internacionales. OCYT. C/ José Abascal, 4. 28003 Madrid. SPAIN
scientific research in such a way that the immediate Ferro, Esteban. Facultad de Ciencias Químicas. Universidad
financial aspects are not considered to be of primary Nacional de Asunción. Fac. de Ciencias Químicas. Dirección de
interest but rather only a legitimate, longer-term Investigación. Departamento de Fitoquímica. Campus
consequence of such partnering8,9. Universitario. San Lorenzo. PARAGUAY.
Ø Since all of humanity benefits from the discovery of new Fischer, Janos. Richter Co., Ltd. P.O. Box 27. H- 1475
drugs, all societies should collaborate in the preservation Budapest, 10. HUNGARY
and evaluation of the areas of great diversity from which Gattuso, Martha. Universidad Nacional de Rosario. Fac.
such structures might emerge. This could be carried out Ciencias Bioquímicas y Farmacéuticas. Biología Vegetal.
through investments made by pharmaceutical companies to Suipacha, 531. 2000 Rosario, ARGENTINA
help preserve this type of land (e.g. of great biodiversity, Gattuso, Susana. Universidad Nacional de Rosario. Fac.
of fragile environment, or where promising species prosper) Ciencias Bioquímicas y Farmacéuticas. Biología Vegetal.
and through the promotion of localized searches done in Suipacha, 531. 2000 Rosario, ARGENTINA
collaborative settings that can allow for both immediate Guccione Salvatore. University of Catania (Italy),
development of identified actives and sustained cultivation Dipartimento di Scienze Farmaceutiche, viale A. Doria 6, Ed.
of undefined biodiversity. 12 Città Universitaria, I-95125 Catania. ITALY
Huenchuñir Gómez, Patricio. Facultad de Medicina,
ADDITIONAL RECOMMENDATIONS Universidad de los Andes. San Carlos de Apoquindo 2200.
6782468. Las Condes. Santiago. CHILE. (RIIDDMED - CYTED).
Ø Strengthen international relationships on these types of Kobayashi, Toshi. PhRMA-Japan. SB Building. 6
research projects, particularly including countries at Sanbancho. Chiyodaku. Tokyo. 102-0075. JAPAN
different levels of development. Martín, Yolanda. Dpto. Química. Universidad Europea de
Madrid. Villaviciosa de Odón. 28670 Madrid. SPAIN.
Ø Utilize university-company relationships within less-
(RIIDDMED - CYTED).
developed countries. Ochoa de Ocáriz, Carmen. Instituto de Química Médica. Juan
Ø Strengthen international relationships between scientists and de la Cierva, 3. 28006-Madrid. SPAIN. (RIIDDMED - CYTED).
the authorities responsible for research in various countries. Sener, Bilge. Director. Department of Pharmacognosy.
Faculty of Pharmacy. Gazi University. P.K. 143. 06572
ACKNOWLEDGMENTS Mattope. Ankara. TURKEY.
Vega Noverola, Salvador. Instituto de Química Médica. Juan
The following persons have collaborated in this work. (May de la Cierva, 3. 28006-Madrid. SPAIN. (RIIDDMED - CYTED).
2, 2000) Zacchino, Susana. Universidad Nacional de Rosario. Fac.
Alcudia González, Felipe. Departamento de Química Ciencias Bioquímicas y Farmacéuticas. Farmacognosia. Suipacha,
Orgánica y Farmacéutica. Universidad de Sevilla, 41012 531. 2000 Rosario, ARGENTINA. (RIIDDMED - CYTED).
Sevilla, SPAIN (Red Iberoamericana de Investigación, Diseño
y Desarrollo de Medicamentos [ RIIDDMED] - CYTED) REFERENCES
Aldana, Ignacio. Dpto. Química Orgánica. Facultad de
Farmacia. Universidad de Navarra. C/ Irunlarrea, s/n. 31008 1. Andrews, P. R.; Borris, R.; Dagne, E.; Gupta, M.; Mistcher,
Pamplona. SPAIN L. A.; Monge, A.; de Souza, N. J. and Topliss, J. G.; Chem.
Benaim, Marisela. Laboratorios GIEMPI. C/ Bolivar. Urb. Int. 1997, 19, 77. (Summary of Technical Report).
La Trinidad - Edif. Klinos .Apdo. Postal 87085. Caracas 1081. 2. Andrews, P. R.; Borris, R.; Dagne, E.; Gupta, M.; Mistcher,
VENEZUELA (RIIDDMED - CYTED). L. A.; Monge, A.; de Souza, N. J. and Topliss, J. G.; Chem.
Cerecetto, Hugo. Facultad de Química y Ciencias. Int. 1997, 19, 77. (Summary of Technical Report)
Universidad de la República. Montevideo. URUGUAY. 3. Monge, A.; Ganellin, R.; Ide, J.; Koga, N.; Mitscher, L.;
(RIIDDMED - CYTED). Muller, C.; Perun, T. J.; Topliss J. G. and Wermuth, C.
Compagnone, Reinaldo S. Escuela de Química. Facultad G.; Chem. Int. 1999, 21, 65.
de Ciencias. Universidad Central de Venezuela. Apdo. 47102. 4. The Phuket Declaration. Chem. Int. 1998, 20, 139.
Caracas. VENEZUELA. (RIIDDMED - CYTED). 5. Borman, S; C&EN 1999, 77, 49
Chiriboga P, Ximena. Universidad Central del Ecuador. 6. Quéan, P.; Fuentes (UNESCO) 1999, 117, 4.
Facultad de Ciencias químicas. Departamento de Fitoquimica 7. R. Pidgeon, R.; Chem. Br. 1999, 35, 25.
y Productos Naturales. Salazar Gómez No N32 – 01 y Martínez 8. Nettleton Jr., D. E.; (DN&P). Drugs, News and Perspectives
.Mera. Quito. ECUADOR. (RIIDDMED - CYTED). 1995, 8, 250.
Domínguez, José N. Universidad Central de Venezuela. 9. Rodríguez, C. M.; “Legal Issues: Contracts, Intellectual
Facultad de Farmacia. Apdo. 40109.Nva. Granada. Caracas. property rights and other property rights”, pp. 183-190, in
VENEZUELA. (RIIDDMED - CYTED). “Biodiversity, Biotechnology and Sustainable Development,
Farré, Antonio J. Lab. Dr. Esteve. M.D.D.Montserrat 221. in Health and Agriculture: Emerging Connections”. Edt.:
08041 Barcelona. SPAIN. (RIIDDMED - CYTED). Organización Panamericana de la Salud, (OPS) Director de
Fernández Braña, Miguel. Universidad San Pablo Ceu. la publicación: George A.O. Alleyne; Washington 1996.