The Anti‐Leishmanial Effects of Compounds Derived from the Fungus Geosmithia langdonii on Visceral Leishmaniasis

Leishmaniasis is among seven of the most prominent tropical diseases and is the second most prevalent parasitic killer after malaria. Existing treatments are often highly toxic to infected patients and must be taken intravenously in hospitalization. These current treatments also have lost viability due to increasing drug resistance. A more cost‐efficient and less harmful treatment urgently needs to be identified. Diarylmethanes have been shown to have many benefits including HIV treatment, cancer treatment, antibacterial activity, and antioxidant activity. A diarylmethane isolated from the fungus Geosmithia langdonii has shown activity against Leishmaniasis. We plan to synthesize this metabolite and similar compounds with varying moieties at different positions to test the significance of these functional groups against Leishmaniasis and to identify an understanding of how these compounds inhibit this parasites’ growth. We were able to successfully grow and propagate Leishmaniasis donovani in M199 media. We also were able to successfully infect human THP1 macrophages and screen several commercially available diarylmethanes, bis(2‐hydroxyphenyl) methane and bis(4‐hydroxyphenyl) methane, by staining for A2, an amastigote specific protein, by indirect immunofluorescence. Results of these two diarylmethanes were compared to a positive control, Amphotericin B, and were shown to have ineffective inhibition of the parasite. Current work is focused on the synthesis of the fungal metabolite and other derivatives. This work will allow us to determine how the structure of these compounds is related to antiparasitic activity. We will utilize what we learn in these experiments to develop more effective treatments for Leishmaniasis.