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Plant-Derived Agents against Cancer and Malaria

16.06.2010
African plants of the Asphodelaceae family contain interesting natural substances: In laboratory tests, some of them were shown to act as agents against malaria pathogens and tumor cells. Professor Gerhard Bringmann of the University of Würzburg studies these natural substances in cooperation with the universities of Johannesburg (South Africa) and Nairobi (Kenya).

The African-German research team has isolated several potential antimalarial and anti-tumor agents from these plants, clarifying their respective chemical structure. These medically interesting substances are called phenyl anthraquinones. They can be found, for instance, in plants of the Kniphofia or Bulbine genus. These plants are native to Africa with a wide distribution in South Africa. There are also some horticultural forms of Kniphofia that are grown as ornamental plants in European gardens.

Gerhard Bringmann: "Phenyl anthraquinones represent a quite remarkable category of natural substances: These molecules consist of two parts, which are connected to each other via an axis." This axis cannot freely rotate so that there are several mirror image forms of the molecules, which can differ in their biological effects.

Active against leukemia and malaria

All phenyl anthraquinones have a certain component in common, which is also present in some other anti-tumor agents. This led to the assumption that phenyl anthraquinones should also have the potential to act as an agent against cancer cells.

"In laboratory tests, some of these substances, e.g knipholone, exhibited an excellent inhibitory activity against certain leukemia cells," says Bringmann. The effect is actually comparable with that of etoposide, which is an established drug in cancer therapy.

In laboratory test sequences, some of these natural substances also stood out in that they were active against the malaria pathogen Plasmodium falciparum. Among other things, this unicellular parasite attacks the red blood cells in the human organism.

Structures clarified, syntheses implemented

The medically interesting effects of the phenyl anthraquinones were discovered at the Collaborative Research Center 630 of the University of Würzburg, the objective of which is the recognition, preparation and functional analysis of agents against infectious diseases; Gerhard Bringmann is its spokesperson.

In the recent years, the natural product chemists of the University of Würzburg have worked very hard to clarify the three-dimensional structure of the phenyl anthraquinones and to produce these substances synthetically. Among the highlights of their work was the discovery of the so-called dimeric anthraquinones: In this case, two of the molecules join together. Furthermore, Bringmann proudly reports on the first-time laboratory synthesis of a whole series of knipholone-type agents.

"Due to our research, the number of the known phenyl anthraquinones has increased from five to more than 20," says the Würzburg professor. However, the substances of many Kniphofia and Bulbine species have not yet been examined or require further research. To change this fact is a central project target of the research triangle "Johannesburg – Nairobi – Würzburg".

Specialist fields of the African partners

The South African research partners, headed by Professor Ben-Erik Van Wyk in Johannesburg, are concerned with the botanical relationships and the taxonomic classification of the plants – they are acknowledged as world-leading experts in this field. The scientific exchange with the South Africans is still in its early stages.

In contrast, mutual visits organized in cooperation with the Kenyan research group of Professor Abiy Yenesew have been established for a long time. This group wants to combine the knowledge of traditional indigenous medicine with the research results in plant chemistry, thus contributing to the pharmaceutical exploitation of African medicinal plants.

So far, nearly 100 plant species have been compiled and botanically characterized by the Kenyan researchers. They have subjected about 25 of these plants to chemical analyses at the laboratories in Nairobi and Würzburg in a joint project funded by the German Research Foundation (DFG). In this process, some new phenyl anthraquinones derived from certain Kniphofia and Bulbine species were discovered and structurally identified.

Macromolecule with fascinating characteristics

"The Asphodelaceae plants still hold many secrets, the discovery of which will keep us busy for a long time," says Gerhard Bringmann. Current examinations give rise to the assumption that the plants can connect as many as four phenyl anthraquinone molecules to form one "macromolecule". This is a particularly fascinating finding. Due to its special three-dimensional structure, the molecule might be able to interact with enzymes or with the genetic code (DNA) – a favorable characteristic for any future medical applications.

A long way to go in the development of new drugs

However, the development of new drugs implies a long, difficult, time-consuming and cost-intensive process. "We can still not predict whether the phenyl anthraquinones will reach the stage of pharmaceutical development and finally make it to the clinical trials," says Bringmann.

Nevertheless, the research triangle "Johannesburg – Nairobi –Würzburg" intends to identify further candidates for future drugs. Such network projects are important: According to Bringmann, the number of new drug approvals has been stagnating for years, although there is a great need for new medicinal agents and therapeutic concepts. After all, millions of people die from malaria or cancer every single year.

Robert Emmerich | idw
Further information:
http://www.uni-wuerzburg.de/

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