A nature-inspired design yields a new class of steroids against trypanosomatids

This article belongs to the Special Issue Drug Discovery for Neglected DiseasesChagas disease and Leishmaniasis are neglected endemic protozoan diseases recognized as public health problems by the World Health Organization. These diseases affect millions of people around the world however, efficient and low-cost treatments are not available. Different steroid molecules with antimicrobial and antiparasitic activity were isolated from diverse organisms (ticks, plants, fungi). These molecules have complex structures that make de novo synthesis extremely difficult. In this work, we designed new and simpler compounds with antiparasitic potential inspired in natural steroids and synthesized a series of nineteen steroidal arylideneketones and thiazolidenehydrazines. We explored their biological activity against Leishmania infantum, Leishmania amazonensis, and Trypanosoma cruzi in vitro and in vivo. We also assayed their genotoxicity and acute toxicity in vitro and in mice. The best compound, a steroidal thiosemicarbazone compound 8 (ID_1260) was active in vitro (IC50 200 nM) and in vivo (60% infection reduction at 50 mg/kg) in Leishmania and T. cruzi. It also has low toxicity in vitro and in vivo (LD50 >2000 mg/kg) and no genotoxic effects, being a promising compound for anti-trypanosomatid drug development

Multi-anti-parasitic activity of arylidene ketones and thiazolidene hydrazines against trypanosoma cruzi and Leishmania spp.

A series of fifty arylideneketones and thiazolidenehydrazines was evaluated against Leishmania infantum and Leishmania braziliensis. Furthermore, new simplified thiazolidenehydrazine derivatives were evaluated against Trypanosoma cruzi. The cytotoxicity of the active compounds on non-infected fibroblasts or macrophages was established in vitro to evaluate the selectivity of their anti-parasitic effects. Seven thiazolidenehydrazine derivatives and ten arylideneketones had good activity against the three parasites. The IC50 values for T. cruzi and Leishmania spp. ranged from 90 nM–25 μM. Eight compounds had multi-trypanocidal activity against T. cruzi and Leishmania spp. (the etiological agents of cutaneous and visceral forms). The selectivity of these active compounds was better than the three reference drugs: benznidazole, glucantime and miltefosine. They also had low toxicity when tested in vivo on zebrafish. Trying to understand the mechanism of action of these compounds, two possible molecular targets were investigated: triosephosphate isomerase and cruzipain. We also used a molecular stripping approach to elucidate the minimal structural requirements for their anti-T. cruzi activity

Hapalopus aymara a new species of tarantula from Bolivia (Araneae, Theraphosidae, Theraphosinae)

A new species of Hapalopus Ausserer, 1875 (Araneae, Theraphosidae, Theraphosinae) from Bolivia is described and illustrated, based in males and females

Spiderling emergence in the tarantula Grammostola mollicoma (Ausserer 1875): an experimental approach (Araneae, Theraphosidae)

Volume: 37Start Page: 92End Page: 9

Is more better? Sexual confusion during courtship between two sympatric and synchronic tarantulas: Acanthoscurria suina and Eupalaestrus weijenberghi

When two similar species co-occur in time and space, strong mechanisms isolating them from each other are expected. Acanthoscurria suina Pocock, 1903 and Eupalaestrus weijenberghi (Thorell, 1894) are two sympatric and synchronic tarantulas that inhabit burrows in Uruguay's meadows. Here we test how and when reproductive isolation operates between these species. We exposed females of each species simultaneously to two males: either one male of each species, or two males of the same species. Males courted females of both species. Contrary to expectations, however, females of A. suina responded more effusively to heterospecific than to conspecific males, whereas females of E. weijenberghi only responded to conspecific males. Clasping (prelude of mating) was only recorded for couples of the same species. Females of A. suina at first seem to prefer the stronger body vibrations performed by heterospecific courting males than by males of their own species

Third pair of legs is a key feature for eliciting female receptivity in the road tarantula spider Eupalaestrus weijenberghi (Araneae: Theraphosidae)

Volume: 41Start Page: 213End Page: 21

Multi-Anti-Parasitic Activity of Arylidene Ketones and Thiazolidene Hydrazines against Trypanosoma cruzi and Leishmania spp.

A series of fifty arylideneketones and thiazolidenehydrazines was evaluated against Leishmania infantum and Leishmania braziliensis. Furthermore, new simplified thiazolidenehydrazine derivatives were evaluated against Trypanosoma cruzi. The cytotoxicity of the active compounds on non-infected fibroblasts or macrophages was established in vitro to evaluate the selectivity of their anti-parasitic effects. Seven thiazolidenehydrazine derivatives and ten arylideneketones had good activity against the three parasites. The IC50 values for T. cruzi and Leishmania spp. ranged from 90 nM–25 µM. Eight compounds had multi-trypanocidal activity against T. cruzi and Leishmania spp. (the etiological agents of cutaneous and visceral forms). The selectivity of these active compounds was better than the three reference drugs: benznidazole, glucantime and miltefosine. They also had low toxicity when tested in vivo on zebrafish. Trying to understand the mechanism of action of these compounds, two possible molecular targets were investigated: triosephosphate isomerase and cruzipain. We also used a molecular stripping approach to elucidate the minimal structural requirements for their anti-T. cruzi activity