*4.4. Antiparasitic Secondary Metabolites*

Cota et al. [108] isolated altenusin from an *Alternaria* sp. endophytic in *Trixis vauthieri* collected in Brazil (Figure 5). This medicinal plant was reported as containing trypanocidal compounds of trypanothione reductase inhibitory activity. Meanwhile, the organic extract of the culture of *Alternaria* sp. inhibited trypanothione reductase by 99%, when tested at 20 mg mL<sup>−</sup>1. The mentioned report was the first one concerning fungal metabolites with trypanothione reductase inhibitory activity, which can be used for the development of new chemotherapeutic agents to treat trypanosomiasis and leishmaniasis. *Trypanosoma cruzi* is a parasitic euglenoid causing Chagas disease in humans, and *Leishmania tarentolae* is a protozoan parasite of geckos, which might also be capable of infecting mammals [125]. Verza et al. [112] determined that endophytic fungus *Phomopsis* sp., obtained from *Viguiera arenaria* (synonym of *Aldama arenaria*), led to the formation of a new compound able to transform the tetrahydrofuran lignan, (−)-grandisin to 3,4-dimethyl-2-(4 -hydroxy-3 ,5 -dimethoxy phenyl)-5-methoxy-tetrahydrofuran, which also showed trypanocidal activity against *T. cruzi*. Guimarães et al. [105] isolated 30 endophytic fungi from the leaves and four from the roots of *V. arenaria* and five endophytes were isolated from the leaves of *Tithonia diversifolia*, collected in Brazil. The ethyl acetate extract of the *Diaporthe phaseolorum* isolate's fermentation broth showed strong inhibition of glyceraldehyde 3-phosphate dehydrogenase of *T. cruzi* and adenine phosphoribosyltransferase of *L. tarentolae*. The mosquito *Culex quinquefasciatus* acts as a vector of *Wuchereria bancrofti* which causes the disease lymphatic filariasis, commonly known as elephantiasis. Belonging to the Asteraceae family, *Ageratum conyzoides,* native to Pakistan, has antilarvicidal effects against the mosquito larvae of *C. quinquefasciatus*, *Aedes aegypti*, and *Anopheles stephensi*. Endophytic actinomycetes, *Streptomyces* spp., isolated from mentioned Asteraceae species showed strong larvicidal activity at the fourth instar stage [126]. Xanthones, sterigmatocystin, and anthraquinone derivative, 13-hydroxyversicolorin B from the culture broth of the endophytic fungus *Podospora* sp., isolated from the Kenyan medicinal plant *Laggera alata*, might be used as natural mosquito larvicides [91]. The easily biodegradable endophyte metabolites could be a base for the development of modern techniques providing efficient insect control, without negative effects on the non-target population and environment.

**Figure 5.** The molecular structure of chosen specific compounds with antiparasitic activity synthesized by fungal endophytes associated with Asteraceae species [91,108,112].
