Bisphosphonate-based molecules as potential new antiparasitic drugs

Neglected tropical diseases such as Chagas disease and leishmaniasis affect millions of people around the world. Both diseases affect various parts of the globe and drugs traditionally used in therapy against these diseases have limitations, especially with regard to low efficacy and high toxicity. In this context, the class of bisphosphonate-based compounds has made significant advances regarding the chemical synthesis process as well as the pharmacological properties attributed to these compounds. Among this spectrum of pharmacological activity, bisphosphonate compounds with antiparasitic activity stand out, especially in the treatment of Chagas disease and leishmaniasis caused by Trypanosoma cruzi and Leishmania spp., respectively. Some bisphosphonate compounds can inhibit the mevalonate pathway, an essential metabolic pathway, by interfering with the synthesis of ergosterol, a sterol responsible for the growth and viability of these parasites. Therefore, this review aims to present the information about the importance of these compounds as antiparasitic agents and as potential new drugs to treat Chagas disease and leishmaniasis.publishersversionpublishe

Evaluation of in vitro Antifungal Activity of Xylosma prockia (Turcz.) Turcz. (Salicaceae) Leaves Against Cryptococcus spp.

Cryptococcus species are responsible for important systemic mycosis and are estimated to cause millions of new cases annually. The available therapy is limited due to the high toxicity and the increasing rates of yeast resistance to antifungal drugs. Popularly known as “sucará,” Xylosma prockia (Turcz.) Turcz. (Salicaceae) is a native plant from Brazil with little information on its pharmacological potential. In this work, we evaluated in vitro anticryptococcal effects of the leaf ethanolic extract of X. prockia and its fractions against Cryptococcus gattii and Cryptococcus neoformans. We also evaluated phenotypic alterations caused by ethyl acetate fraction (EAF) (chosen according to its biological results). The liquid chromatography–mass spectrometry (LC-MS) analysis of EAF demonstrated the presence of phenolic metabolites that belong to three structurally related groups as majority compounds: caffeoylquinic acid, coumaroyl-glucoside, and caffeoyl-glucoside/deoxyhexosyl-caffeoyl glucoside derivatives. The minimum inhibitory concentration (MIC) values against C. gattii and C. neoformans ranged from 8 to 64 mg/L and from 0.5 to 8 mg/L, for ethanolic extract and EAF, respectively. The EAF triggered an oxidative burst and promoted lipid peroxidation. EAF also induced a reduction of ergosterol content in the pathogen cell membrane. These effects were not associated with alterations in the cell surface charge or in the thermodynamic fingerprint of the molecular interaction between EAF and the yeasts evaluated. Cytotoxic experiments with peripheral blood mononuclear cells (PBMCs) demonstrated that EAF was more selective for yeasts than was PBMCs. The results may provide evidence that X. prockia leaf extract might indeed be a potential source of antifungal agents.Fil: Folly, Mariany L. C.. Universidade Federal de Juiz de Fora; BrasilFil: Ferreira, Gabriella F.. Universidade Federal de Juiz de Fora; BrasilFil: Salvador, Maiara R.. Universidade Federal de Juiz de Fora; BrasilFil: Sathler, Ana A.. Universidade Federal de Juiz de Fora; BrasilFil: da Silva, Guilherme F.. Universidade Federal de Juiz de Fora; BrasilFil: Santos, Joice Castelo Branco. Ceuma University; BrasilFil: Santos, Julliana R. A. dos. Ceuma University; BrasilFil: Nunes Neto, Wallace Ribeiro. Ceuma University; BrasilFil: Rodrigues, João Francisco Silva. Ceuma University; BrasilFil: Fernandes, Elizabeth Soares. Ceuma University; BrasilFil: da Silva, Luís Cláudio Nascimento. Ceuma University; BrasilFil: de Freitas, Gustavo José Cota. Universidade Federal de Minas Gerais; BrasilFil: Denadai, Ângelo M.. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas; BrasilFil: Rodrigues, Ivanildes V.. Universidade Federal de Juiz de Fora; BrasilFil: Mendonça, Leonardo M.. Universidade Federal de Juiz de Fora; BrasilFil: Monteiro, Andrea Souza. Ceuma University; BrasilFil: Santos, Daniel Assis. Universidade Federal de Minas Gerais; BrasilFil: Cabrera, Gabriela Myriam. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; ArgentinaFil: Siless, Gastón Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; ArgentinaFil: Lang, Karen L.. Universidade Federal de Juiz de Fora; Brasi