Inspired by nature

Biodiversity is still an endless source of new molecular architecture for the development of medicines, cosmetics and agrichemicals, say researchers.

By Elton Alisson

Agência FAPESP – Nearly 200 years after the discovery of morphine—which was isolated for the first time in 1804 by German pharmacist Friedrich Wilhelm Adam Serturner from the Papaver somniferum—the pharmaceutical industry has discovered a peptide from the toxin of the marine mollusk Conus magus that, with just a few structural modifications, becomes more potent than the analgesic and some of its derivatives used in the treatment of chronic pain.

Approved in 2004 by the Food and Drug Administration (FDA) – the United States’ food and drug regulatory agency – and released under the brand name Prialt, the synthetic version of the marine mollusk’s active principal is an illustrative example of how biodiversity continues to be an endless source of new molecular architecture for the development of new drugs, cosmetics and agrichemical products.

The evaluation was made by Vanderlan da Silva Bolzani, professor at the Universidade Estadual Paulista (Unesp) Institute of Chemistry and coordinator of BIOTA-FAPESP, in a lecture on “Biodiversity & Chemistry” that she presented on July 19 at the fourth meeting of the International Year of Chemistry Conference Series, held in the FAPESP auditorium.

According to Bolzani, after the advent of the post-genome era 15 years ago, speculations began as to whether the pharmaceutical industry would lose interest in natural products as the sector began to use new technology for development of drugs. The prediction didn’t come true, however, and natural products continue to grow as sources of ideas as they provide unforeseen chemical structural models for the development of new bioactive substances.

“The majority of today’s new molecular entities are completely derived from or inspired by natural products. The land and marine environments continue to be inexhaustible sources of chemical structures,” she said.

A recent international study substantiates the claim: of the 847 low molecular weight drugs (micromolecules) released on the market between 1981 and 2006, 43 were products in their natural form, 232 produced by hemisynthesis (part of their structure being derived from nature and another part developed in laboratory) based on natural products and 572 were derived from total synthesis, 262 of which were inspired by natural products or could be considered analogous to natural products.

One of these is nitisinone, an active compound discovered by Swiss pharmacists in the Callistemon citrinus L. Myrtaceae plant, which is used today for treatment of a rare metabolic disorder called hereditary tyrosinemia type 1.

Released on the market in 2002 under the Orfadin brand name, the drug is also a good example of how Brazil loses opportunities to exploit its rich biodiversity for the development of new pharmaceutical, cosmetic and agrichemical products, pointed out Bolzani.

“With the quantity of Myrtaceae we have in our biodiversity, it would be possible for Brazil to develop many similar medications. We would produce great riches if there were a favorable environment not only for basic research, but also for the development of better regulatory measures,” she affirmed.

The researcher’s opinion was shared by Carlos Alfredo Joly, full professor at the Universidade Estadual de Campinas (Unicamp) and coordinator of the BIOTA-FAPESP program. According to him, Brazilian legislation is the largest obstacle to the good economic use of national studies and development of natural products.

“In spite of our rich biodiversity, Brazil produces very few new pharmaceuticals. One part of this problem is structural and the other has to do with legislation that regulates the access to genetic resources in the country, a provisional measure that has been in effect for 11 years carrying a series of requirements that have made the process of obtaining licenses and authorizations needed to work on the identification of new molecules torturesome,” he affirmed.

According to the researcher, this obstacle to development in the field of chemistry of natural products that the legislation represents was one of the reasons he accepted the invitation to take over as Director of the Department of Policies and Thematic Programs (DPPT) in the Ministry of Science and Technology’s Secretariat of Research and Development Policies and Programs.

The researcher says that since he took the position, he has been dedicated to the elaboration of legislation that regulates access to genetic resources in Brazil that already incorporates the resolutions from the Nagoya Protocol. 

Approved during the Convention on Biological Diversity’s 10th meeting of the Conference of the Parties (COP10) held in Japan in October 2010, the protocol establishes rules for division of the benefits of genetic resources originating in a nation’s biodiversity.

“The convention was very tenuous and the protocol is much more incisive in terms of protecting nations holding biodiversity. With new Brazilian legislation on access to genetic resources based on the Nagoya Protocol, it’s hoped that we’ll have the conditions to conduct research inside Brazil that results in greater potential for utilization of our biodiversity,” he evaluated.

According to Joly, the transformation of biodiversity resources into value is also one of the objectives of the BIOTA-FAPESP program which, since it was started in 1999, has been systematically inventorying biodiversity in the State of São Paulo.

In order to increase the possibility of transforming the economic potential of local biodiversity resources into something concrete, the program will increase its bioprospection division, mainly in marine biodiversity. 

“In BIOTA-FAPESP, we’re not just looking at bioprospection of plants and land vertebrates, but also mostly studying marine algae and invertebrates. This is an extremely promising new area that has been growing successfully the world over and that we need to increase,” he said.