Session Speaker

Global Challenges for New Drug Discovery against Tropical Parasitic Diseases: Multidirectional Molecular Targets-Based Strategies
Babu L. Tekwani and Larry A Walker
USA

The parasitic diseases namely, malaria, leishmaniases and trypanosomiases (new and old world) are responsible for staggering morbidity and millions of deaths every year, especially in the tropical regions. More than half of the world’s population is currently under the risk of being exposed to the infection with one or the other tropical disease pathogens. Emergence and spread of drug-resistant and more virulent strains of the parasites have further intensified the problem. Despite of the heavy burden on humanity the tropical parasitic diseases have been mostly ignored in relation to advances in modern drug discovery and only few new antiparasitic drugs have been developed during last several years. Improved funding with recent attention of non-profit organizations and emergence of public-private partnerships for development of strategies to treat neglected tropical parasitic diseases has generated unprecedented interests in new antiparasitic drug discovery programs. Completion of parasite genome projects have resulted into increased interests to study and identify unique metabolic pathways of these pathogens. A major outcome of these efforts has been the availability of large number of novel and validated molecular targets for new drug discovery. In many therapeutic areas, such targets would have served as a platform from which the pharmaceutical industry would have mounted an extensive screening campaign to identify potential new drug leads. However, in the case of tropical diseases the commercial potential is not sufficiently attractive to entice companies to invest in such campaigns. Recent consortium efforts among different laboratories have created the scopes for pooling expensive sophisticated resources required for modern high efficiency drug discovery programs. An initiative by WHO tropical diseases research (TDR) program on compilation of diverse datasets should facilitate the identification and prioritization of drug targets in the pathogens. The TDR Targets database (tdrtargets.org) provides information on the pathogen targets of interest, which can be exploited as a tool for prioritization of druggable targets. The parasite genome data-bases have been significant expanded and are constantly updated to access the most recent data on the targets. National Institute of Health USA has initiated a program on molecular libraries roadmap and high throughput screening. We have adopted a multidirectional targets-based approach for new antiparasitic drug discovery. This involves random screening of compound libraries through a battery of validated target enzymes, development and evaluation of selective targeted compound libraries and application of lead compounds with novel structures to probe chemotherapeutic targets. The new antiparasitic leads are followed through a critical path paradigm- in silico analysis, in vitro ADME profiling, in vivo preclinical evaluation for efficacy and toxicity, and optimization of leads through preparation of analogs. These efforts have significantly enriched the antiparasitic drug discovery pipeline with novel pharmacophores.