Synthesis and biological evaluation of novel imidazolidine derivatives as candidates to schistosomicidal agents

Introduction: Schistosomiasis is an infectious parasitic disease caused by trematodes of the genus Schistosoma, which threatens at least 258 million people worldwide and its control is dependent on a single drug, praziquantel. The aim of this study was to evaluate the anti-Schistosoma mansoni activity in vitro of novel imidazolidine derivatives. Material and methods: We synthesized two novel imidazolidine derivatives: (LPSF/PTS10) (Z)-1-(2-chloro-6-fluorobenzyl)-4-(4-dimethylaminobenzylidene)-5-thioxoimidazolidin-2-one and (LPSF/PTS23) (Z)-1-(2-chloro-6-fluoro-benzyl)-5-thioxo-4-(2,4,6-trimethoxy-benzylidene)-imidazolidin-2-one. The structures of two compounds were determined by spectroscopic methods. During the biological assays, parameters such as motility, oviposition, mortality and analysis by Scanning Electron Microscopy were performed. Results: LPSF/PTS10 and LPSF/PTS23 were considered to be active in the separation of coupled pairs, mortality and to decrease the motor activity. In addition, LPSF/PTS23 induced ultrastructural alterations in worms, after 24 h of contact, causing extensive erosion over the entire body of the worms. Conclusion: The imidazolidine derivatives containing the trimetoxy and benzylidene halogens showed promising in vitro schistosomicidal activity

ULTRASTRUCTURAL CHANGES IN Schistosoma mansoni MALE WORMS AFTER in vitro INCUBATION WITH THE ESSENTIAL OIL OF Mentha x villosa Huds

Introduction: The essential oil Mentha x villosa (MVEO) has a wide range of actions, including antibacterial, antifungal, antiprotozoal and schistosomicidal actions. The present study aimed to investigate the ultrastructural changes of MVEO on the tegument of adult Schistosoma mansoni. Materials and Methods: Different concentrations of MVEO were tested on S. mansoni adult worms in vitro. Ultrastructural changes on the tegument of these adult worms were evaluated using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Results: The MVEO caused the death of all worms at 500 μg mL-1 after 24 h. After 24h of 500 μg mL-1 MVEO treatment, bubble lesions were observed over the entire body of worms and they presented loss of tubercles in some regions of the ventral portion. In the evaluation by TEM, S. mansoni adult worms treated with MVEO, 500 μg mL-1, presented changes in the tegument and vacuoles in the syncytial matrix region. Glycogen granules close to the muscle fibers were visible. Conclusion: The ability of MVEO to cause extensive ultrastructural damage to S. mansoni adult worms correlates with its schistosomicidal effects and confirms earlier findings with S. mansoni

Potencial terapêutico de novos fármacos na avaliação da atividade esquistossomicida

A esquistossomose mansoni, considerada um grave problema de saúde pública, é causada por vermes tremátodas da espécie Schistosoma mansoni. A forma de tratamento dessa parasitose baseia-se principalmente na quimioterapia, onde o fármaco de escolha utilizado atualmente é o praziquantel que se destaca dentre os outros agentes esquistossomicidas por ser eficaz contra todas as espécies de Schistosoma. No entanto, a utilização exclusiva do praziquantel no tratamento da esquistossomose mansoni tem ocasionado a base do desenvolvimento de uma possível resistência dos vermes do S. mansoni a esse fármaco, surgindo à necessidade da busca de novos fármacos esquistossomicidas que sirvam como alternativa para o tratamento da parasitose. Neste contexto, estudos vêm destacando os derivados tiazolidínicos como potenciais esquistossomicidas através da citotoxicidade e da avaliação da susceptibilidade de vermes adultos do S. mansoni mantidos in vitro e in vivo. Neste trabalho, testamos a atividade esquistossomicida dos derivados tiazolidínicos LPSF/SF-03, LPSF/SF-05, LPSF/SF-20 e LPSF/SF-22 e LPSF/SF-25 em diferentes concentrações (100μg/mL, 80μg/mL, 60μg/mL e 40μg/mL). O praziquantel foi utilizado como o fármaco controle. Observamos que os compostos LPSF/SF-22 e o LPSF/SF-25 apresentaram melhor atividade in vitro frente aos vermes adultos do Schistosoma mansoni na dose de 80μg/mL com uma taxa de mortalidade de 70% e 86%, respectivamente. Nos ensaios de citotoxicidade, o derivado tiazolidínico LPSF/SF-25 apresentou uma melhor concentração atóxica quando comparados aos outros derivados tiazolidínicos testados. Visto aos resultados obtidos in vitro com o composto LPSF/SF-25, este derivado foi testado in vivo, apresentando uma redução de 28% do número de vermes adultos do S. mansoni e alterações nos estádios evolutivos dos ovos dos parasitos. Dessa forma, sugere-se que o derivado tiazolidínico LPSF/SF-25 pode ser considerado um potencial candidato a fármaco esquistossomicid

INVESTIGAÇÃO EPIDEMIOLÓGICA DAS PRINCIPAIS DOENÇAS INFECCIOSAS E PARASITÁRIAS EXISTENTES NO MUNICÍPIO DE PAULO AFONSO, ESTADO DA BAHIA E BRASIL

<p>Doenças infecciosas e parasitáras (DIP's), causadas por parasitas que tem potencial transmissor, ainda representam um problema de saúde pública. É preciso conhecer seu perfil epidemiológico para combatê-las. Este trabalho tem como objetivo conhecer a epidemiologia das principais DIP's no município de Paulo Afonso entre os anos de 2014 a 2018 e posteriormente compará-la com o estado da Bahia e com o Brasil. Para isso, foram utilizados dados secundários contidos no site do Departamento de Informática do Sistema Único de Saúde (DATASUS) que foram analisados usando o Software SPSS 22.0. Os resultados revelaram que as principais DIP's no município foram tuberculose, dengue e hanseníase. A tuberculose apresentou pouca variação na taxa de incidência entre os anos estudados. A dengue teve um aumento nos anos de 2015 e 2016 sofrendo um redução nos anos seguinte. Ambas as doenças foram mais representativas no Brasil quando comparadas a Paulo Afonso. Por outro lado, a hanseníase apresentou variações significativas sendo as maiores taxas encontradas em Paulo Afonso. Os dados demonstram a necessidade de adotar medidas para alcançar efetivamente na contenção das doenças.</p&gt

Synthesis and biological evaluation of novel imidazolidine derivatives as candidates to schistosomicidal agents

ABSTRACT Introduction: Schistosomiasis is an infectious parasitic disease caused by trematodes of the genus Schistosoma, which threatens at least 258 million people worldwide and its control is dependent on a single drug, praziquantel. The aim of this study was to evaluate the anti-Schistosoma mansoni activity in vitro of novel imidazolidine derivatives. Material and methods: We synthesized two novel imidazolidine derivatives: (LPSF/PTS10) (Z)-1-(2-chloro-6-fluorobenzyl)-4-(4-dimethylaminobenzylidene)-5-thioxoimidazolidin-2-one and (LPSF/PTS23) (Z)-1-(2-chloro-6-fluoro-benzyl)-5-thioxo-4-(2,4,6-trimethoxy-benzylidene)-imidazolidin-2-one. The structures of two compounds were determined by spectroscopic methods. During the biological assays, parameters such as motility, oviposition, mortality and analysis by Scanning Electron Microscopy were performed. Results: LPSF/PTS10 and LPSF/PTS23 were considered to be active in the separation of coupled pairs, mortality and to decrease the motor activity. In addition, LPSF/PTS23 induced ultrastructural alterations in worms, after 24 h of contact, causing extensive erosion over the entire body of the worms. Conclusion: The imidazolidine derivatives containing the trimetoxy and benzylidene halogens showed promising in vitro schistosomicidal activity

Tegumental changes in adult Schistosoma mansoni induced by a new imidazolidinic derivative

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2015-05-26T18:35:45Z No. of bitstreams: 1 Silva AL Tegumental....pdf: 1075054 bytes, checksum: 84c8b45a8a8b55f686120c9ac3597428 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-05-26T18:50:36Z (GMT) No. of bitstreams: 1 Silva AL Tegumental....pdf: 1075054 bytes, checksum: 84c8b45a8a8b55f686120c9ac3597428 (MD5)Made available in DSpace on 2015-05-26T18:50:36Z (GMT). No. of bitstreams: 1 Silva AL Tegumental....pdf: 1075054 bytes, checksum: 84c8b45a8a8b55f686120c9ac3597428 (MD5) Previous issue date: 2014Federal University of Pernambuco. Institute of Biology. Department of Antibiotics. Recife, PE, BrasilFundação Oswaldo Cruz, Centro de Pesquisas Aggeu Magalhães. Laboratório of Immunology and Molecular Biology. Recife, PE, BrasilFederal University of Pernambuco. Institute of Biology. Department of Antibiotics. Recife, PE, BrasilFundação Oswaldo Cruz, Centro de Pesquisas Aggeu Magalhães. Laboratório of Immunology and Molecular Biology. Recife, PE, BrasilFederal University of Pernambuco. Institute of Biology. Department of Antibiotics. Recife, PE, BrasilFederal University of Pernambuco. Institute of Biology. Department of Antibiotics. Recife, PE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Laboratório de Ultraestrutura. Departmento de Entomologia. Recife, PE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, BrasilFederal University of Pernambuco. Institute of Biology. Department of Antibiotics. Recife, PE, BrasilFederal University of Pernambuco. Institute of Biology. Department of Antibiotics. Recife, PE, BrasilAims: Verify the potential of the schistosomicidal imidazolidine derivative (5Z)-3-(4- bromo-benzyl)-5-(4-chloro-benzylidene)-4-thioxo-imidazolidin-2-one. Study Design: In this study, we tested the imidazolidinic derivative 3 through in vitro evaluations, cytotoxicity assay and analysis of Scanning Electron Microscopy to verify its therapeutic potential in the treatment of schistosomiasis. Place and Duration of Study: Departamento de Antibióticos, Universidade Federal de Pernambuco (UFPE), Fundação Oswaldo Cruz (FIOCRUZ)/PE and (FIOCRUZ)/BA between January 2013 and march 2014. Methodology: This study was approved by the Ethics Committee on Animal Use Research Center Aggeu Magalhães/Oswaldo Cruz Fundação (CPqAM/FIOCRUZ) authorized by the license No. 21/2011. Male albino Swiss mice were used Mus musculus 25 days old weighing 50 grams. Compound 3 was assayed for its cytotoxicity through cell J774 macrophage lineage. The amount of inhibitory concentration (LC50) was determined by nonlinear regression using the Graph Pad Prism version 5.01. Then the compound was evaluated against adult worms of S. mansoni by performing the activity in vitro at doses 100-20μg/mL and ultrastructural investigation by Scanning Electron Microscopy (SEM) at doses of 100 and 60μg/ml. The PZQ was the positive control of the experiment. Results: The derivative 3 showed LC50 of 29.7±3.9mM. Compound 3 was able to have decreased motility of S. mansoni culminating with a mortality rate of 100% at doses of 60 and 100μg/mL on the fourth day of observation of the experiment. In the SEM, the compound caused various soft tissue changes of S. mansoni parasites such as blistering, destruction of the integument with loss of spines and tubercles, body contraction and windy. Conclusion: The derivative imidazolidine 3 showed a promising schistosomicidal activity in vitro. However, conducting further studies with the completion of work in front of the live schistosomiasis is required

Evaluation of the anti-Schistosoma mansoni activity of thiosemicarbazones and thiazoles

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-04-03T13:26:17Z No. of bitstreams: 1 Santiago EF Evaluation of the anti-Schistosoma ....pdf: 4333306 bytes, checksum: 0a4eafc14622c78b28659cb69c2c2996 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-04-03T14:24:14Z (GMT) No. of bitstreams: 1 Santiago EF Evaluation of the anti-Schistosoma ....pdf: 4333306 bytes, checksum: 0a4eafc14622c78b28659cb69c2c2996 (MD5)Made available in DSpace on 2018-04-03T14:24:14Z (GMT). No. of bitstreams: 1 Santiago EF Evaluation of the anti-Schistosoma ....pdf: 4333306 bytes, checksum: 0a4eafc14622c78b28659cb69c2c2996 (MD5) Previous issue date: 2014Conselho Nacional de Desenvolvimento Científico e Tecnológico (CPNq) and Fundação Oswaldo Cruz (FIOCRUZ). FAPESB postdoctoral scholarship.Federal University of Pernambuco. Department of Pharmacy. Recife, PE, Brazil / Federal University of Pernambuco. Laboratory of Immunopathology. Recife, PE, BrazilFederal University of Pernambuco. Laboratory of Immunopathology. Recife, PE, BrazilFederal University of Pernambuco. Department of Pharmacy. Recife, PE, BrazilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFederal University of Pernambuco. Department of Pharmacy. Recife, PE, BrazilFederal University of Pernambuco. Laboratory of Immunopathology. Recife, PE, BrazilFederal University of Pernambuco. Laboratory of Immunopathology. Recife, PE, BrazilFederal University of Pernambuco. Laboratory of Immunogenetics. Recife, PE, BrazilFederal University of Pernambuco. Laboratory of Immunogenetics. Recife, PE, BrazilFederal University of Pernambuco. Laboratory of Immunogenetics. Recife, PE, BrazilFundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, BrasilFederal University of Pernambuco. Department of Physiology and Pharmacology. Recife, PE, BrazilFederal University of Pernambuco. Department of Pharmacy. Recife, PE, BrazilSchistosomiasis is a chronic and debilitating disease caused by a trematode of the genus Schistosoma and affects over 207 million people. Chemotherapy is the only immediate recourse for minimizing the prevalence of this disease and involves predominately the administration of a single drug, praziquantel (PZQ). Although PZQ has proven efficacy, there is a recognized need to develop new drugs as schistosomicides since studies have shown that repeated use of this drug in areas of endemicity may cause a temporary reduction in susceptibility in isolates of Schistosoma mansoni. Hydrazones, thiosemicarbazones, phthalimides, and thiazoles are thus regarded as privileged structures used for a broad spectrum of activities and are potential candidates for sources of new drug prototypes. The present study determined the in vitro schistosomicidal activity of 10 molecules containing these structures. During the assays, parameters such motility and mortality, oviposition, morphological changes in the tegument, cytotoxicity, and immunomodulatory activity caused by these compounds were evaluated. The results showed that compounds formed of thiazole and phthalimide led to higher mortality of worms, with a significant decline in motility, inhibition of pairing and oviposition, and a mortality rate of 100% starting from 144 h of exposure. These compounds also stimulated the production of nitric oxide and tumor necrosis factor alpha (TNF-α), thereby demonstrating the presence of immunomodulatory activity. The phthalyl thiazole LpQM-45 caused significant ultrastructural alterations, with destruction of the tegument in both male and female worms. According to the present study, phthalyl thiazole compounds possess antischistosomal activities and should form the basis for future experimental and clinical trials