Antiprotozoal action of synthetic cinnamic acid analogs

Submitted by EMERSON LEAL ([email protected]) on 2019-09-13T15:06:29Z No. of bitstreams: 1 Antiprotozoal action of synthetic cinnamic acid analogs.pdf: 1282999 bytes, checksum: 9055bccde66932ebd2ae36450ab4d6f5 (MD5)Approved for entry into archive by EMERSON LEAL ([email protected]) on 2019-09-13T15:27:30Z (GMT) No. of bitstreams: 1 Antiprotozoal action of synthetic cinnamic acid analogs.pdf: 1282999 bytes, checksum: 9055bccde66932ebd2ae36450ab4d6f5 (MD5)Made available in DSpace on 2019-09-13T15:27:30Z (GMT). No. of bitstreams: 1 Antiprotozoal action of synthetic cinnamic acid analogs.pdf: 1282999 bytes, checksum: 9055bccde66932ebd2ae36450ab4d6f5 (MD5) Previous issue date: 2018Fundação Oswaldo Cruz. Plataforma de Bioensaios em Malária e Leishmaniose. Porto Velho, RO, Brasil. / Universidade Federal de Rondônia. Programa de Pós-graduação em Biologia Experimental. Porto Velho, RO, Brasil. / Universidade Federal de Rondônia. Centro de Estudos de Biomoléculas Aplicadas à Saúde. Porto Velho, RO, Brasil.Fundação Oswaldo Cruz. Plataforma de Bioensaios em Malária e Leishmaniose. Porto Velho, RO, Brasil. / Centro Universitário São Lucas. Porto Velho, RO, Brasil.Fundação Oswaldo Cruz. Plataforma de Bioensaios em Malária e Leishmaniose. Porto Velho, RO, Brasil. / Universidade Federal de Rondônia. Programa de Pós-graduação em Biologia Experimental. Porto Velho, RO, Brasil. / Universidade Federal de Rondônia. Centro de Estudos de Biomoléculas Aplicadas à Saúde. Porto Velho, RO, Brasil.Universidade Federal de Rondônia. Programa de Pós-graduação em Biologia Experimental. Porto Velho, RO, Brasil. / Universidade Federal de Rondônia. Centro de Estudos de Biomoléculas Aplicadas à Saúde. Porto Velho, RO, Brasil. / Centro para el Desarrollo de Investigación Científica. Asunción, Paraguay.Universidade Federal de Rondônia. Programa de Pós-graduação em Biologia Experimental. Porto Velho, RO, Brasil. / Universidade Federal de Rondônia. Centro de Estudos de Biomoléculas Aplicadas à Saúde. Porto Velho, RO, Brasil. / Centro para el Desarrollo de Investigación Científica. Asunción, Paraguay.Centro para el Desarrollo de Investigación Científica. Asunción, Paraguay.Fundação Oswaldo Cruz. Plataforma de Bioensaios em Malária e Leishmaniose. Porto Velho, RO, Brasil. / Universidade Federal de Rondônia. Programa de Pós-graduação em Biologia Experimental. Porto Velho, RO, Brasil. / Centro Universitário São Lucas. Porto Velho, RO, Brasil. / Instituto Nacional de Epidemiologia na Amazônia Ocidental. Porto Velho, RO, Brasil.Fundação Oswaldo Cruz. Plataforma de Bioensaios em Malária e Leishmaniose. Porto Velho, RO, Brasil. / Universidade Federal de Rondônia. Programa de Pós-graduação em Biologia Experimental. Porto Velho, RO, Brasil. / Universidade Federal de Rondônia. Centro de Estudos de Biomoléculas Aplicadas à Saúde. Porto Velho, RO, Brasil.Introduction: Leishmaniasis, Chagas disease, and malaria cause morbidity globally. The drugs currently used for treatment have limitations. Activity of cinnamic acid analogs against Leishmania spp., Trypanosoma cruzi, and Plasmodium falciparum was evaluated in the interest of identifying new antiprotozoal compounds. Methods: In vitro effects of analogs against L. braziliensis, L. infantum chagasi, T. cruzi, and P. falciparum, and hemolytic and cytotoxic activities on NCTC 929 were determined. Results: Three analogs showed leishmanicidal and tripanocidal activity. No antiplasmodial, hemolytic, or cytotoxic activity was observed. Conclusions: Antiprotozoal activity of analogs against L. infantum braziliensis, L. infantum chagasi, and T. cruzi was demonstrated

Synergism of in vitro plasmodicidal activity of phospholipase A2 isoforms isolated from panamanian Bothrops asper venom

Bothrops asper is one of the most important snake species in Central America, mainly because of its medical importance in countries like Ecuador, Panama and Costa Rica, where this species causes a high number of snakebite accidents. Several basic phospholipases A2 (PLA2s) have been previously characterized from B. asper venom, but few studies have been carried out with its acidic isoforms. In addition, since snake venom is a rich source of bioactive substances, it is necessary to investigate the biotechnological potential of its components. In this context, this study aimed to carry out the biochemical characterization of PLA2 isoforms isolated from B. asper venom and to evaluate the antiparasitic potential of these toxins. The venom and key fractions were subjected to different chromatographic steps, obtaining nine PLA2s, four acidic ones (BaspAc-I, BaspAc-II, BaspAc-III and BaspAc-IV) and five basic ones (BaspB-I, BaspB-II, BaspB-III, BaspB-IV and BaspB-V). The isoelectric points of the acidic PLA2s were also determined, which presented values ranging between 4.5 and 5. The findings indicated the isolation of five unpublished isoforms, four Asp49-PLA, corresponding to the group of acidic isoforms, and one Lys49-PLA2-like. Acidic PLA2s catalyzed the degradation of all substrates evaluated; however, for the basic PLA2s, there was a preference for phosphatidylglycerol and phosphatidic acid. The antiparasitic potential of the toxins was evaluated, and the acidic PLA2s demonstrated action against the epimastigote forms of T. cruzi and promastigote forms of L. infantum, while the basic PLA2s BaspB-II and BaspB-IV showed activity against P. falciparum. The results indicated an increase of up to 10 times in antiplasmodial activity, when the Asp49-PLA2 and Lys49-PLA2 were associated with one another, denoting synergistic action between these PLA2 isoforms. These findings correspond to the first report of synergistic antiplasmodial action for svPLA2s, demonstrating that these molecules may be important targets in the search for new antiparasitic agent