The Experts below are selected from a list of 93 Experts worldwide ranked by ideXlab platform
Daniel B Roquini - One of the best experts on this subject based on the ideXlab platform.
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promethazine exhibits antiparasitic properties in vitro and reduces worm burden egg production hepatomegaly and splenomegaly in a schistosomiasis animal model
Antimicrobial Agents and Chemotherapy, 2019Co-Authors: Daniel B Roquini, Ramon M Cogo, Ana C Mengarda, Susana F Mazloum, Cristiane S Morais, Rogerio P Xavier, M C Salvadori, F S Teixeira, Luiz E Ferreira, Pedro L S PintoAbstract:: The treatment and control of schistosomiasis, a neglected disease that affects more than 200 million people worldwide, rely on the use of a single drug, praziquantel. A vaccine has yet to be developed and since new drug design and development is a lengthy and costly process, drug repurposing is a promising strategy. In this study, the efficacy of promethazine, a first-generation antihistamine, was evaluated against Schistosoma mansoniex vivo and in a murine model of schistosomiasis. In vitro assays demonstrated that promethazine affected parasite motility, viability, and it induced severe tegumental damage in schistosomes. The LC50 of the drug was 5.84 μM. Similar to promethazine, schistosomes incubated with atropine, a classical anticholinergic drug, displayed reduced motor activity. In an animal model, promethazine treatment was introduced at an oral dose of 100 mg/kg for five successive days at different intervals from the time of infection, for the evaluation of the stage-specific susceptibility (pre-patent and patent infections). Various parasitological criteria indicated the in vivo Antischistosomal effects of promethazine: there were significant reductions in worm burden, egg production, and hepato- and splenomegaly. The highest worm burden reduction was achieved with promethazine in patent infections (> 90%). Taken together, considering the importance of the repositioning of drugs in infectious diseases, especially those related to poverty, our data revealed the possibility of promethazine repositioning as an Antischistosomal Agent.
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Promethazine exhibits antiparasitic properties in vitro and reduces worm burden, egg production, hepato-, and splenomegaly in a schistosomiasis animal model.
Antimicrobial agents and chemotherapy, 2019Co-Authors: Daniel B Roquini, Ramon M Cogo, Ana C Mengarda, Susana F Mazloum, Cristiane S Morais, Luiz E Ferreira, R. Xavier, Maria Cecília Barbosa Da Silveira Salvadori, Fernanda De Sá Teixeira, Pedro L S PintoAbstract:The treatment and control of schistosomiasis, a neglected disease that affects more than 200 million people worldwide, rely on the use of a single drug, praziquantel. A vaccine has yet to be developed and since new drug design and development is a lengthy and costly process, drug repurposing is a promising strategy. In this study, the efficacy of promethazine, a first-generation antihistamine, was evaluated against Schistosoma mansoni ex vivo and in a murine model of schistosomiasis. In vitro assays demonstrated that promethazine affected parasite motility, viability, and it induced severe tegumental damage in schistosomes. The LC50 of the drug was 5.84 μM. Similar to promethazine, schistosomes incubated with atropine, a classical anticholinergic drug, displayed reduced motor activity. In an animal model, promethazine treatment was introduced at an oral dose of 100 mg/kg for five successive days at different intervals from the time of infection, for the evaluation of the stage-specific susceptibility (pre-patent and patent infections). Various parasitological criteria indicated the in vivo Antischistosomal effects of promethazine: there were significant reductions in worm burden, egg production, and hepato- and splenomegaly. The highest worm burden reduction was achieved with promethazine in patent infections (> 90%). Taken together, considering the importance of the repositioning of drugs in infectious diseases, especially those related to poverty, our data revealed the possibility of promethazine repositioning as an Antischistosomal Agent.
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vanillin related n acylhydrazones synthesis Antischistosomal properties and target fishing studies
Current Topics in Medicinal Chemistry, 2019Co-Authors: Daniela Goncales Rando, Marcos P Silva, Marcela Oliveira Legramanti Da Costa, Thais Fernanda Amorim Pavani, Thiago Pouso Oliveira, Paloma Freire Dos Santos, Carina R Amorim, Pedro Luiz Silva Pinto, Mariana Brito, Daniel B RoquiniAbstract:Background Schistosomiasis is a neglected disease, which affects millions of people in developing countries. Its treatment relies on a single therapeutic alternative, the praziquantel. This situation may lead to drug resistance which, in turn, made urgent the need for new Antischistosomal Agents. Nacylhydrazones are usually explored as good antimicrobial Agents, but the vanillin-related N-acylhydrazones have never been tested by their antiparasitic potential. Objective Herein, we report the synthesis of seven analogues, three of them unpublished, their biological investigation against Schistosoma mansoni and Target Fishing studies. Methods The compounds were synthesized following classical synthetical approaches. The anthelmintic potential was assessed as well as their cytotoxicity profile. Confocal laser scanning microscopy and target fishing study were performed to better understand the observed Antischistosomal activity. Results Compound GPQF-407 exhibited good Antischistosomal activity (47.91 µM) with suitable selectivity index (4.14). Confocal laser scanning microscopy revealed that it triggered severe tegumental destruction and tubercle disintegration. Target fishing studies pointed out some probable targets, such as the serine-threonine kinases, dihydroorotate dehydrogenases and carbonic anhydrase II. Conclusion The GPQF-407 was revealed to be a promising Antischistosomal Agent which, besides presenting the N-acylhydrazone privileged scaffold, also could be easily synthesized on large scales from commercially available materials.
Pedro L S Pinto - One of the best experts on this subject based on the ideXlab platform.
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promethazine exhibits antiparasitic properties in vitro and reduces worm burden egg production hepatomegaly and splenomegaly in a schistosomiasis animal model
Antimicrobial Agents and Chemotherapy, 2019Co-Authors: Daniel B Roquini, Ramon M Cogo, Ana C Mengarda, Susana F Mazloum, Cristiane S Morais, Rogerio P Xavier, M C Salvadori, F S Teixeira, Luiz E Ferreira, Pedro L S PintoAbstract:: The treatment and control of schistosomiasis, a neglected disease that affects more than 200 million people worldwide, rely on the use of a single drug, praziquantel. A vaccine has yet to be developed and since new drug design and development is a lengthy and costly process, drug repurposing is a promising strategy. In this study, the efficacy of promethazine, a first-generation antihistamine, was evaluated against Schistosoma mansoniex vivo and in a murine model of schistosomiasis. In vitro assays demonstrated that promethazine affected parasite motility, viability, and it induced severe tegumental damage in schistosomes. The LC50 of the drug was 5.84 μM. Similar to promethazine, schistosomes incubated with atropine, a classical anticholinergic drug, displayed reduced motor activity. In an animal model, promethazine treatment was introduced at an oral dose of 100 mg/kg for five successive days at different intervals from the time of infection, for the evaluation of the stage-specific susceptibility (pre-patent and patent infections). Various parasitological criteria indicated the in vivo Antischistosomal effects of promethazine: there were significant reductions in worm burden, egg production, and hepato- and splenomegaly. The highest worm burden reduction was achieved with promethazine in patent infections (> 90%). Taken together, considering the importance of the repositioning of drugs in infectious diseases, especially those related to poverty, our data revealed the possibility of promethazine repositioning as an Antischistosomal Agent.
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Promethazine exhibits antiparasitic properties in vitro and reduces worm burden, egg production, hepato-, and splenomegaly in a schistosomiasis animal model.
Antimicrobial agents and chemotherapy, 2019Co-Authors: Daniel B Roquini, Ramon M Cogo, Ana C Mengarda, Susana F Mazloum, Cristiane S Morais, Luiz E Ferreira, R. Xavier, Maria Cecília Barbosa Da Silveira Salvadori, Fernanda De Sá Teixeira, Pedro L S PintoAbstract:The treatment and control of schistosomiasis, a neglected disease that affects more than 200 million people worldwide, rely on the use of a single drug, praziquantel. A vaccine has yet to be developed and since new drug design and development is a lengthy and costly process, drug repurposing is a promising strategy. In this study, the efficacy of promethazine, a first-generation antihistamine, was evaluated against Schistosoma mansoni ex vivo and in a murine model of schistosomiasis. In vitro assays demonstrated that promethazine affected parasite motility, viability, and it induced severe tegumental damage in schistosomes. The LC50 of the drug was 5.84 μM. Similar to promethazine, schistosomes incubated with atropine, a classical anticholinergic drug, displayed reduced motor activity. In an animal model, promethazine treatment was introduced at an oral dose of 100 mg/kg for five successive days at different intervals from the time of infection, for the evaluation of the stage-specific susceptibility (pre-patent and patent infections). Various parasitological criteria indicated the in vivo Antischistosomal effects of promethazine: there were significant reductions in worm burden, egg production, and hepato- and splenomegaly. The highest worm burden reduction was achieved with promethazine in patent infections (> 90%). Taken together, considering the importance of the repositioning of drugs in infectious diseases, especially those related to poverty, our data revealed the possibility of promethazine repositioning as an Antischistosomal Agent.
Ana C Mengarda - One of the best experts on this subject based on the ideXlab platform.
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new evidence for tamoxifen as an Antischistosomal Agent in vitro in vivo and target fishing studies
Future Medicinal Chemistry, 2021Co-Authors: Tais C Silva, Ana C Mengarda, M C Salvadori, F S Teixeira, Daniela Goncales Rando, Bianca C Silva, Thais S Relvaslima, Vinicius C Rodrigues, Andrey F S Lopes, Josue De MoraesAbstract:Background: Praziquantel is the only drug available to treat schistosomiasis, and there is an urgent demand for new anthelmintic Agents. Methodology & results: We conducted in-depth in vitro and in...
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Antiparasitic Properties of Cardiovascular Agents against Human Intravascular Parasite Schistosoma mansoni
'MDPI AG', 2021Co-Authors: Raquel Porto, Ana C Mengarda, Rayssa A. Cajas, Maria C. Salvadori, Fernanda S. Teixeira, Daniel D. R. Arcanjo, Abolghasem Siyadatpanah, Maria De Lourdes Pereira, Polrat Wilairatana, Josue De MoraesAbstract:The intravascular parasitic worm Schistosoma mansoni is a causative Agent of schistosomiasis, a disease of great global public health significance. Praziquantel is the only drug available to treat schistosomiasis and there is an urgent demand for new anthelmintic Agents. Adopting a phenotypic drug screening strategy, here, we evaluated the antiparasitic properties of 46 commercially available cardiovascular drugs against S. mansoni. From these screenings, we found that amiodarone, telmisartan, propafenone, methyldopa, and doxazosin affected the viability of schistosomes in vitro, with effective concentrations of 50% (EC50) and 90% (EC90) values ranging from 8 to 50 µM. These results were further supported by scanning electron microscopy analysis. Subsequently, the most effective drug (amiodarone) was further tested in a murine model of schistosomiasis for both early and chronic S. mansoni infections using a single oral dose of 400 mg/kg or 100 mg/kg daily for five consecutive days. Amiodarone had a low efficacy in chronic infection, with the worm and egg burden reduction ranging from 10 to 30%. In contrast, amiodarone caused a significant reduction in worm and egg burden in early infection (>50%). Comparatively, treatment with amiodarone is more effective in early infection than praziquantel, demonstrating the potential role of this cardiovascular drug as an Antischistosomal Agent
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promethazine exhibits antiparasitic properties in vitro and reduces worm burden egg production hepatomegaly and splenomegaly in a schistosomiasis animal model
Antimicrobial Agents and Chemotherapy, 2019Co-Authors: Daniel B Roquini, Ramon M Cogo, Ana C Mengarda, Susana F Mazloum, Cristiane S Morais, Rogerio P Xavier, M C Salvadori, F S Teixeira, Luiz E Ferreira, Pedro L S PintoAbstract:: The treatment and control of schistosomiasis, a neglected disease that affects more than 200 million people worldwide, rely on the use of a single drug, praziquantel. A vaccine has yet to be developed and since new drug design and development is a lengthy and costly process, drug repurposing is a promising strategy. In this study, the efficacy of promethazine, a first-generation antihistamine, was evaluated against Schistosoma mansoniex vivo and in a murine model of schistosomiasis. In vitro assays demonstrated that promethazine affected parasite motility, viability, and it induced severe tegumental damage in schistosomes. The LC50 of the drug was 5.84 μM. Similar to promethazine, schistosomes incubated with atropine, a classical anticholinergic drug, displayed reduced motor activity. In an animal model, promethazine treatment was introduced at an oral dose of 100 mg/kg for five successive days at different intervals from the time of infection, for the evaluation of the stage-specific susceptibility (pre-patent and patent infections). Various parasitological criteria indicated the in vivo Antischistosomal effects of promethazine: there were significant reductions in worm burden, egg production, and hepato- and splenomegaly. The highest worm burden reduction was achieved with promethazine in patent infections (> 90%). Taken together, considering the importance of the repositioning of drugs in infectious diseases, especially those related to poverty, our data revealed the possibility of promethazine repositioning as an Antischistosomal Agent.
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Promethazine exhibits antiparasitic properties in vitro and reduces worm burden, egg production, hepato-, and splenomegaly in a schistosomiasis animal model.
Antimicrobial agents and chemotherapy, 2019Co-Authors: Daniel B Roquini, Ramon M Cogo, Ana C Mengarda, Susana F Mazloum, Cristiane S Morais, Luiz E Ferreira, R. Xavier, Maria Cecília Barbosa Da Silveira Salvadori, Fernanda De Sá Teixeira, Pedro L S PintoAbstract:The treatment and control of schistosomiasis, a neglected disease that affects more than 200 million people worldwide, rely on the use of a single drug, praziquantel. A vaccine has yet to be developed and since new drug design and development is a lengthy and costly process, drug repurposing is a promising strategy. In this study, the efficacy of promethazine, a first-generation antihistamine, was evaluated against Schistosoma mansoni ex vivo and in a murine model of schistosomiasis. In vitro assays demonstrated that promethazine affected parasite motility, viability, and it induced severe tegumental damage in schistosomes. The LC50 of the drug was 5.84 μM. Similar to promethazine, schistosomes incubated with atropine, a classical anticholinergic drug, displayed reduced motor activity. In an animal model, promethazine treatment was introduced at an oral dose of 100 mg/kg for five successive days at different intervals from the time of infection, for the evaluation of the stage-specific susceptibility (pre-patent and patent infections). Various parasitological criteria indicated the in vivo Antischistosomal effects of promethazine: there were significant reductions in worm burden, egg production, and hepato- and splenomegaly. The highest worm burden reduction was achieved with promethazine in patent infections (> 90%). Taken together, considering the importance of the repositioning of drugs in infectious diseases, especially those related to poverty, our data revealed the possibility of promethazine repositioning as an Antischistosomal Agent.
Thomas W Kensler - One of the best experts on this subject based on the ideXlab platform.
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role of phase 2 enzyme induction in chemoprotection by dithiolethiones
Mutation Research, 2001Co-Authors: Mi Kyoung Kwak, Patricia A Egner, Patrick Dolan, Minerva Ramosgomez, John D Groopman, Ken Itoh, Masayuki Yamamoto, Thomas W KenslerAbstract:One of the major mechanisms of protection against carcinogenesis, mutagenesis, and other forms of toxicity mediated by carcinogens is the induction of enzymes involved in their metabolism, particularly phase 2 enzymes such as glutathione S-transferases (GSTs), UDP-glucuronosyl transferases, and quinone reductases. Animal studies indicate that induction of phase 2 enzymes is a sufficient condition for obtaining chemoprevention and can be achieved by administering any of a diverse array of naturally-occurring and synthetic chemopreventive Agents. Indeed, monitoring of enzyme induction has led to the recognition or isolation of novel, potent chemopreventive Agents such as 1,2-dithiole-3-thiones, terpenoids and the isothiocyanate sulforaphane. For example, oltipraz, a substituted 1,2-dithiole-3-thione originally developed as an Antischistosomal Agent, possesses chemopreventive activity against different classes of carcinogens targeting multiple organs. Mechanistic studies in rodent models for chemoprevention of aflatoxin B(1) (AFB(1))-induced hepatocarcinogenesis by oltipraz indicates that increased expression of phase 2 genes is of central importance, although inhibition of phase 1 activation of AFB(1) can also contribute to protection. Exposure of rodents to 1,2-dithiole-3-thiones triggers nuclear accumulation of the transcription factor Nrf2 and its enhanced binding to the "antioxidant response element" (ARE), leading to transcriptional activation of a score of genes involved in carcinogen detoxication and attenuation of oxidative stress. Nrf2-deficient mice fail to induce many of these genes in response to dithiolethiones; moreover, basal expression of these genes is typically repressed. To test the hypothesis that enzyme induction is a useful strategy for chemoprevention in humans, three key elements are necessary: a candidate Agent, an at-risk population and modulatable intermediate endpoints. Towards this end, a placebo-controlled, double blind clinical trial of oltipraz was conducted in residents of Qidong, PR China who are exposed to dietary aflatoxins and who are at high risk for the development of liver cancer. Oltipraz significantly enhanced excretion of a phase 2 product, aflatoxin-mercapturic acid, a derivative of the aflatoxin-glutathione conjugate, in the urine of study participants administered 125 mg oltipraz by mouth daily. Administration of 500 mg oltipraz once a week led to a significant reduction in the excretion of the primary oxidative metabolite of AFB(1), AFM(1), when measured shortly after drug administration. While this study highlighted the general feasibility of inducing phase 2 enzymes in humans, a longer term intervention is addressing whether protective alterations in aflatoxin metabolism can be sustained for extended periods of time in this high-risk population.
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Oltipraz: Clinical opportunities for cancer chemoprevention
Journal of Cellular Biochemistry, 1995Co-Authors: Thomas W Kensler, Kathy J. HelzlsouerAbstract:Oltipraz [4-methyl-5-(2-pyrazinyl)-1,2-dithiole-3-thione], originally developed as an Antischistosomal Agent, protects against chemical carcinogenesis in lung, trachea, forestomach, small intestine, colon, breast, skin, liver and urinary bladder in rodents. Oltipraz induces electrophile detoxication enzymes, resulting in diminished carcinogen-DNA adduct formation and reduced cytotoxicity, an important component of anticarcinogenic actions. Phase I trials of this drug have been recently conducted in the United States and indicate that the maximum tolerated dose is about 125 mg/day over a six-month period. Grade I/II dose-limiting toxicities included photosensitivity/heat intolerance, gastrointestinal, and neurologic toxicities. Ongoing studies are monitoring relationships between dose scheduling, drug plasma concentrations and pharmacodynamic action. Subsequent trials with this Agent might most appropriately target individuals at high risk for occupational or environmental exposures to genotoxic carcinogens. Towards this end, a randomized, placebo-controlled Phase II study is planned for people at high risk for exposure to aflatoxins and development of hepatocellular carcinoma. Modulation of biomarkers reflecting the biologically effective dose of aflatoxin will serve as study endpoints.
S S Althagfan - One of the best experts on this subject based on the ideXlab platform.
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eugenol a potential schistosomicidal Agent with anti inflammatory and antifibrotic effects against schistosoma mansoni induced liver pathology
Infection and Drug Resistance, 2019Co-Authors: Asmaa M Elkady, El-deek Hem, Alzahraa Abdelraouf Ahmad, Tasneem M Hassan, S S Fouad, S S AlthagfanAbstract:Introduction Schistosomiasis is one of the most prevalent parasitic infections in developing countries. Although chemotherapy is one of the main strategies in controlling the disease, it is less effective in reversal of schistosome-induced pathology especially in the chronic and advanced stages of schistosomiasis. New strategies and prospective therapeutic Agents with antifibrotic effects are needed. Eugenol has a wide anti-inflammatory effect. In the present study, we investigated the possible Antischistosomal effect of eugenol on Schistosoma mansoni. Materials and methods The murine model of S. mansoni was established in three groups of adult male Balb-c mice; group I (infected non-treated group) and groups II and III (infected groups) treated orally with eugenol and praziquantel (PZQ), respectively. The expression of the sensitive immunohistochemical marker α-smooth muscle actin (α-SMA) in schistosome-infected tissues was determined. In addition, parasitological, biochemical, and histological parameters that reflect disease severity and morbidity were examined. Results Eugenol treatment showed significant reduction in total worm burden by 19.2%; however, the oogram pattern showed no marked difference compared to that of the PZQ group. Yet, eugenol significantly reduced the serum levels of hepatic enzymes: aspartate aminotransferase and alanine aminotransferase. Histopathological examination revealed a significant reduction in both numbers and diameters of hepatic granulomata, which was consistent with reduction in collagen fiber deposition. Additionally, the antifibrotic effect of eugenol was validated by its considerable reduction in the expression of the sensitive marker α-SMA in both eugenol- and PZQ-treated groups. Conclusion Although eugenol could not totally eradicate adults of S. mansoni, the significant amelioration of liver enzymes and hepatic fibrosis potentiate eugenol's role as a promising antifibrotic and a complementary Antischistosomal Agent.