[Opening Lecture] – Natural products and drug discovery for tropical diseases – successes, failures and lessons learned

Infectious diseases of poverty are responsible for countless deaths and enormous disability in tropical and sub-tropical regions of the planet. Current treatments include natural products and synthetic drugs, but many of these are unsatisfactory for reasons such as toxicity, poor efficacy and safety, the need for hospitalisation, lack of oral bioavailability, drug resistance and high cost. Lack of investment due to poor economic return has been a major disincentive for the pharmaceutical industry to venture into drug discovery for neglected diseases. To try to overcome this obstacle, several academic groups are now engaged in early stage drug discovery (up to preclinical candidate) in order to maximise the chances of success by de-risking discovery projects. Some of the successes, failures and lessons learned by the Drug Discovery Unit and by my own laboratory will be presented, with examples from phenotypic- and target-based projects in malaria, sleeping sickness, visceral leishmaniasis and Chagas' disease.