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ANTIMAL

Source: TropIKA

Title of the session: ANTIMAL

Date: 3/11/2009

Agenda item: Symposium 13

Session theme: Early drug discovery

Meeting room: Amphitheatre

Chair(s): Steve Ward, Liverpool School of Tropical Medicine

Presenters:

• Chibale Kelly, Department of Chemistry and Institute of infectious disease and Molecular Medicine, South Africa
• Steve Ward for Pat Bray, Liverpool School of Tropical Medicine
• Bousejra-El Garah Fatima, Department of Chemistry, University of Liverpool
• Mimche Patrice, London School of Hygiene and Tropical Medicine
• Abdi Abdirahman, University of Glasgow
• Dr. Nzila Alexis, KEMRI/Welcome Trust Laboratories
• Kaniti Archana, Liverpool School of Tropical Medicine
• Barton Victoria, Liverpool University
• Adama Gansane

TropIKA rapporteur: Beatrice Irungu

Major topics:

• Discovering & developing antimalarial drugs in Africa by Africans: challenges & opportunities
• Targeting mutant PfCRT in antimalarial drug development
• Role of heme in the antimalarial activity of peroxide containing drugs
• Potential of Methotrexate in the treatment of malaria
• Multiple targets of antimalarial bis-cations and delayed parasite death

Keywords:

• Drug discovery
• malaria
• Plasmodium falciparum

Scope:

• Developing antimalarial compounds from natural products and also from synthetic compounds
• Discovering new antimalarial drug targets

REPORT ON ORIGINAL SESSION

Overview

ANTIMAL, a EU funded project began in December 2005. Its main objective is to exploit new scientific and political opportunities to secure the development of a portfolio of viable novel antimalarial drugs. It is an integrated project comprising of leading groups of researchers with expertise in malaria biology, chemotherapy and drug development. This symposium focused on early drug discovery projects. Areas covered include development of new drugs against novel targets, modification of existing drug templates and novel uses for existing drugs.

CONTEXT AND ISSUE

Malaria still remains a public health problem with children below five years and pregnant women being affected most. There is need to search for new molecules active against Plasmodium falciparum. There is also a need to identify new drug targets.

Key facts and figures

Develop new drugs to fight malaria. This will ensure that there will be alternatives to replace the drugs that are currently in use when they eventually lose their efficacy.

Initiatives on the ground; experience/s derived

• Explore natural products for their potential as antimalarial drug leads

• Synthesis of new molecules such as the tetraoxanes, a class of peroxides believed to possess a similar mode of action as artemisinin

• Identify new drug targets

• Screen drugs used for other indications

Lessons learned

It is important for researchers to partner as this will allow them to work with appropriate expertise. Network of partnership helps overcome some limitations inherent in antimalarial drug discovery and development in Africa.

There is a possibility to develop new heme-binding drugs that are more effective than chloroquine as heme is still a great target. Diamidines believed to have a similar mode of action as chloroquine demonstrated good activity against chloroquine resistant lines. Synthetic peroxides were also found to have a similar mode of action as artemisinin.

Use target for other diseases as a target for malaria. For example, Plasmodium falciparum tyrosine-like protein kinases was assessed for its potential as an antimalarial drug target. PfTKL3 and PfKL1 were found to be potential schizonticidal targets. NB protein kinases are targets for cancer chemotherapy

Methotrexate a drug used in cancer chemotherapy was exploited for its potential as an antimalarial drug. It was found to be safe in healthy adult volunteers at low doses.

Issues raised, obstacles, difficulties

• Most compounds have poor oral bioavailability

• Drug discovery takes long time is very expensive and many molecules are required.

• Natural products in Africa are yet to be exploited for health and economic benefits

Future plans

To create technology platform that will allow the exploration of the potential of African natural products to be fed into modern paradigms of drug discovery

Establish a virtual library of natural products isolated from Africa

Develop a data base accessible by collaborators across Africa

FINDINGS AND CONCLUSIONS

From formal presentations

Public health Implications

Development of new antimalarial drugs active against plasmodium resistant strains will contribute in reducing the morbidity and mortality of malaria

Knowledge gap created

Exploiting targets for other diseases as potential targets for malaria is another way of drug discovery. A good example is protein kinases which are targets for cancer chemotherapy. They were assessed for their potential as schizonticidal drug targets

From open discussions/debates

In making an African Biobank it would be advisable for researchers to collected compounds isolated from African plants.

Methotrexate lowers immune system if used on chronic basis. Noted that this will not be the case with malaria

What advantage does methotrexate have over other existing drugs? None

Toxicity of methotrexate; noted that it is used to treat juvenile arthritis and is found to be safe

Recommendations

Natural products researchers should consider using leaves or stem bark instead of roots to conserve medicinal plants

Personal observations from rapporteur

Antimalarial drug discovery is a continuous process. It is important for research to collaborate/partner in their search for new antimalarial drugs as this will help them overcome some limitations inherent in antimalarial drug discovery and development.

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