CADD and Synthesis of Fenarimols for Mycetoma Therapies

Chronic mycetoma, a neglected tropical disease, is a suppurative and inflammatory fungal (eumycetoma) or bacterial (actinomycetoma) infection of cutaneous and subcutaneous tissue. Due to the poor economic situation in most affected countries, mycetoma is neglected and currently treated with medications that are expensive, cytotoxic, or have a poor route of administration. The non-profit organization DNDi (Drugs for Neglected Diseases initiative) engages graduate and undergraduate students in research for potential therapeutics for a variety of under-researched diseases. In collaboration with the DNDi, fenarimol analogs of DNDi's lead compound DNDI0003105207 were synthesized based on a compound found with proven activity in previous trials as a potential anti-eumycetoma therapeutic. Using Computer-Aided Drug Design (CADD), the binding affinities of 17 potential analogs were analyzed and the three analogs with the highest binding affinities were synthesized. Synthesis involved utilizing techniques such as TLC, a work-up, and column chromatography. FTIR (ATR) was used to characterize final compounds, which will be shipped to DNDi collaborators for further testing in biological assays. Based on structure-activity relationship (SAR) information, a second generation of drug discovery efforts of fenarimols will be synthesized.