This is an application for a Fogarty International Research Collaboration Award (FIRCA) between the research groups of Dr. Gloria Serra (Assistant Professor of Medicinal Chemistry, UniversIdad de Ia Republica, Montevideo, Uruguay) and Dr. Peter Wipf (Professor of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA). Our specific aims in this collaborative project are: - Synthesis of bis-oxazoles, bis-oxazolines, bis-thiazoles and bis-thiazolines analogs of the anthelminthic marine natural product bengazole. This is the primary goal of this application. - Evaluation of biological activities, e.g. i) In vitro anthelmintic activity against Nippostrongylus brassiliensis by Prof. Laura DomInguez from the Pharmacology Department of the Faculty of Chemistry (Uruguay); ii) cytotoxic activity in cancer cell lines by Dr. Adriana Baz at the Immunology Department of the Faculty of Chemistry (Uruguay); iii) if the results of the in vitro anthelminthic activity assays are significant, the Pharmacology Department will perform an in vivo evaluation. - SAR analysis of compounds of type 1: i) esterification with fatty acids of some of the 0H groups on the lateral chain; ii) preparation of 0/S heterocycle analogs for structures of type 1; iii) preparation of analogs differing in the level of polyhydroxylation at the lateral chain R. Chemotherapy has been a long-standing effective instrument for battling parasitic infections in both human and veterinary medicine. Although there have been major advances in the clinical treatment of anthelmintic diseases, there are still no ideal broad-spectrum anthelminthics. Moreover, the field has suffered major setbacks, since resistance of nematodes to the anthelminthic drugs of general use such as benzimidazoles levamizole and praziquantel has emerged. The proposed project will provide a wide range of bengazole analogs for testing of their anthelminthic properties which represents a crucial step in the development of new antiparasitic pharmaceuticals.