This joint German-Indonesian project aims at the development of new lead structures for anti-infective drugs from Indonesian plants and associated endophytes. The project will focus on endemic plants and their endophytes from the Mount Halimun Salak National Park. On a yearly basis, a total of 50 extracts from plants and 50 extracts from endophytes will be prepared that will be tested in comprehensive antimicrobial screenings for their anti-infective properties. The antimicrobial screens include cellular assays against HIV, the Malaria parasite Plasmodium falciparum, Mycobacterium tuberculosis as the causative microbe for tuberculosis, and against multi-resistant nosocomial pathogens. Further screens will address molecular targets such as HIV-1 reverse transcriptase, HIV-1 protease and HIV-1 integrase, which are essential for the life-cycle of HIV, as well as the enoyl-ACP reductase, which is involved in fatty acid biosynthesis of Plasmodium falciparum. Extracts that show bioactivity in one or several of these screens will be subjected to bioactivity guided fractionation that will ultimately yield pure active substances showing antibacterial, antiviral or antiparasitic activity. These active compounds will be structurally characterized and evaluated for possible cytotoxicity towards humane cell lines as well as for their pharmacological properties (ADME). It is estimated that these endeavours will ultimately yield 5 – 10 promising compounds with favourable ADME profiles for each indication investigated in this project. These compounds will be subjected to structural optimization through medicinal chemistry methods. It is expected that at the end of the first funding period our consortium will have identified at least one novel lead structure for each of the investigated indications. These compounds can then be further evaluated in preclinical studies during subsequent funding periods.