In vitro and in vivo leishmanicidal and trypanocidal activities of isoflavans from Tabebuia chrysantha (Jacq.) G. Nicholson timber by-products

Cutaneous Leishmaniasis and Chagas disease are neglected tropical diseases that affect millions worldwide. Despite the high morbidity associated with these infections, current treatments are often highly toxic and are showing diminishing efficacy. Thus, new therapeutic options are urgently needed. In this study, bio-guided assays were conducted on the sawdust of Tabebuia chrysantha ("guayacán") to identify promising bioactive compounds. The ethanolic crude extract, five chromatography fractions, pure isoflavans sativan and vestitol, and a mixture were evaluated in vitro against Leishmania braziliensis and Trypanosoma cruzi . High leishmanicidal and trypanocidal activities were observed in the crude extract, fraction F2 (rich in sativan and vestitol), and the two pure isoflavans. Given the abundance and ease of obtaining the isoflavan mixture, its therapeutic potential was further evaluated in vivo in hamsters infected with L. braziliensis and mice infected with T. cruzi . Remarkably, topical and intraperitoneal administration of the chromatography fraction achieved a 67% clinical cure in hamsters with L. braziliensis infection and a 75% reduction in parasitemia in T. cruzi -infected mice. While the antiparasitic effects of certain flavonoids have been documented, this study is the first to demonstrate the efficacy of isoflavans in animal models for both diseases. The potential efficacy observed against T. cruzi and L. braziliensis , two pathogens with limited treatment options and a significant drawback of the available treatments, highlights the therapeutic potential of this combination of sativan and vestitol, which can be derived from timber industry waste, presenting an abundant and accessible source for further development. Extract, fractions, and metabolites (sativan and vestitol) were isolated from the sawdust of Tabebuia chrysanta and evaluated for cytotoxicity, hemolytic activity, and activity against Leishmania braziliensis and Trypanosoma cruzi activity by in vitro and in vivo assays. A fraction containing a mixture of Sativan and Vestitol showed higher antiparasitic activity and lower cytotoxicity than the isolated metabolites, eliminating the need to obtain pure molecules from natural products. • Sawdust from Tabebuia chrysantha (Jacq.) G. Nicholson 1887 wood is an important source of Sativan and Vestitol metabolites. • Sativan and Vestitol have activity against Leishmania braziliensis and Trypanosoma cruzi parasites. • Standardized fractions obtained from natural sources are suitable for therapeutic purposes. • Cytotoxicity of fraction containing Sativan and Vestitol is lower compared to the isolated molecules. • A fraction containing a mixture of Sativan and Vestitol showed higher antiparasitic activity than the isolated metabolites.