Antiparasitic, structural, pharmacokinetic, and toxicological properties of riparin derivatives

Mafud, Ana Carolina; Silva, Marcos P.N.; Nunes, Geandra Batista Lima; Oliveira, Milene Aparecida Rodrigues de; Batista, Larissa Fernandes; Rubio, Thiago I.; Mengarda, Ana C.; Lago, Eloi M; Rathinam, Xavier; Gutierrez, Stanley Juan Chávez; Pinto, Pedro; Filho, Ademar A. Da Silva; Mascarenhas, Yvonne P.; Moraes, Josué de

doi:10.1016/j.tiv.2018.02.012

Cited by 43 publications

(28 citation statements)

References 58 publications

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“…For in vitro antischistosomal assay, one pair of worms was transferred to each well of a 24-well culture plate (tissue culture plastics; TPP, St. Louis, MO) containing RPMI medium supplemented with FCS and antibiotics (100 IU/ml penicillin and 100 g/ml streptomycin) at 37°C in a 5% CO 2 atmosphere as previously described (31,32). The S. mansoni cultures were then incubated with each drug at final concentration of 50 M. Parasites were then kept for 72 h, and the effects of compounds were assessed microscopically, with an emphasis on changes in worm motor activity, morphological changes, and mortality rate.…”

Section: Methodsmentioning

confidence: 99%

In Vitro and In Vivo Studies of Spironolactone as an Antischistosomal Drug Capable of Clinical Repurposing

Guerra

Silva

et al. 2019

Antimicrob Agents Chemother

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Schistosomiasis is a parasitic flatworm disease that infects over 200 million people worldwide, especially in poor communities. Treatment and control of the disease rely on just one drug, praziquantel. Since funding for drug development for poverty-associated diseases is very limited, drug repurposing is a promising strategy. In this study, from a screening of 13 marketed diuretics, we identified that spironolactone, a potassium-sparing diuretic, had potent antischistosomal effects on Schistosoma mansoni in vitro and in vivo in a murine model of schistosomiasis. In vitro, spironolactone at low concentrations (<10 µM) is able to alter worm motor activity and the morphology of adult schistosomes, leading to parasitic death. In vivo, oral treatment with spironolactone at a single dose (400 mg/kg) or daily for five consecutive days (100 mg/kg/day) in mice harboring either patent or prepatent infections significantly reduced worm burden, egg production, and hepato- and splenomegaly (P < 0.05 to P < 0.001). Taken together, with the safety profile of spironolactone, supported by its potential to affect schistosomes, these results indicate that spironolactone could be a potential treatment for schistosomiasis and make it promising for repurposing.

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Section: Methodsmentioning

confidence: 99%

In Vitro and In Vivo Studies of Spironolactone as an Antischistosomal Drug Capable of Clinical Repurposing

Guerra

Silva

et al. 2019

Antimicrob Agents Chemother

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“…The NMR spectroscopic data are in accordance with those of the literature. [27] (E)-2'-Hydroxy-4'-methoxychalcone (6). Obtained from 2-hydroxy-4-methoxyacetophenone and benzaldehyde.…”

Section: Characterization Of Synthesized Compoundsmentioning

confidence: 99%

“…[24] In Vitro Schistosomicidal Assays S. mansoni (BH strain) worms were obtained from Mesocricetus auratus hamsters according to standard procedures described previously by our group. [6] Briefly, hamsters (3 weeks old) were infected by subcutaneous injection of 150 S. mansoni cercariae. After 9 weeks, adults S. mansoni worms were recovered from the animals by perfusion with RPMI 1640 medium supplemented with heparin.…”

Section: Characterization Of Synthesized Compoundsmentioning

confidence: 99%

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In Vitro and in Vivo Antischistosomal Activities of Chalcones

Pereira

Alves

Silveira

et al. 2018

Chemistry & Biodiversity

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In this study, we evaluated the in vitro and in vivo schistosomicidal activities of chalcones against Schistosoma mansoni worms. In vitro assays revealed that chalcones 1 and 3 were the most active compounds, without affecting significantly mammalian cells. Confocal laser scanning microscopy and scanning electron microscopy studies revealed reduction on the numbers of tubercles and morphological alterations in the tegument of S. mansoni worms after in vitro incubation with chalcones 1 and 3. In a mouse model of schistosomiasis, the oral treatment (400 mg/kg) with chalcone 1 or 3 significantly caused a total worm burden reduction in mice. Chalcone 1 showed significant inhibition of the S. mansoni ATP diphosphohydrolase activity, which was corroborated by molecular docking studies. The results suggested that chalcones could be explored as lead compounds with antischistosomal properties.

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“…Synthetic riparin analogues have already demonstrated antioxidant, including analysis of isolated mitochondria of the brain of mice [6,7] , antimicrobial [8] , antiparasitic [9] , as well as leishmanicide [10] , vasodilator [7] and anti-inflammatory [11] activities. Among the properties of synthetic riparins, their action in the Central Nervous System (CNS), such anxiolytic effects [12] in anxiety models, without affecting the locomotion of the animals used in the experiment [7] , which make them target molecules of new studies aimed at obtaining therapeutic alternatives, and can be used in the treatment of AD.…”

Section: Introductionmentioning

confidence: 99%

In-silico studies of Riparin B in the design of drugs: Physicochemical, pharmacokinetic and pharmacodynamic parameters

Rodrigues¹,

Oliveira²,

Costa

et al. 2020

Preprint

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27The process involved in the research, discovery and development of drugs is 28 characterized by high extensive and complex cost linked to scientific and 29 technological innovations, and it is necessary to study and verify the progress of 30 research carried out in the field that results in patent applications. Aniba riparia 31 (Nees) Mez is a plant species often used for therapeutic purposes, where its 32 pharmacological properties are associated to the presence of alkaloids called 33 riparins. 5 synthetic analog compounds (riparins A, B, C, D, E and F) were 34 developed from natural riparins. These molecules, natural and synthetic, showed 35 several pharmacological activities in tests performed in vitro and in vivo, 36 highlighting the Central Nervous System (CNS). The objective of this work was 37 to evaluate the physical-chemical, pharmacokinetic parameters (absorption, 38 distribution, metabolism, excretion and toxicity) and pharmacodynamic 39 parameters (bioactivity and adverse reactions) of Riparin B by means of in silico 40 computational prediction. Online software such as Pre-ADMET, SwissADME, 41 Molinspiration and PASS on line were used for the analysis. Riparin B fits the 42 characteristics of druglikeness, pharmacokinetic properties appropriate to the 43 predicted patterns and activities within the scope for the treatment of AD, 44 demonstrating a possible potential in the inhibition of AChE. Therefore, in silico 45 results allow us to conclude that riparin B is predicted to be a potential future drug 46 candidate, especially via oral administration, due to its relevant Drug-likeness 47 profile, bioavailability, excellent liposolubility and adequate pharmacokinetics,48including at the level of CNS, penetrating the blood-brain barrier. 49 50 73the natural molecules of this species, there are synthetic analogues known as 74 riparins A, B, C, D and F, which share structures similar to natural molecules [5] . 75 4 Synthetic riparin analogues have already demonstrated antioxidant, 76including analysis of isolated mitochondria of the brain of mice [6,7] , antimicrobial [8] , 77 antiparasitic [9] , as well as leishmanicide [10] , vasodilator [7] and anti-inflammatory [11] 78 activities. Among the properties of synthetic riparins, their action in the Central 79Nervous System (CNS), such anxiolytic effects [12] in anxiety models, without 80 affecting the locomotion of the animals used in the experiment [7] , which make 81 them target molecules of new studies aimed at obtaining therapeutic alternatives, 82 and can be used in the treatment of AD. 83However, there is a significant problem that still remains in the drug 84 discovery procedure, particularly in the later stages of conducting research: the 85 analysis of the properties of ADME (absorption, distribution, metabolism and 86 excretion) and the evident toxicity of drug candidates. Over 50% of drug 87 candidates fail due to poor analysis of ADME/Tox during a drug design [2] . 88 To evaluate the physicochemical, pharmacokinetic (absorption,...

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Antiparasitic, structural, pharmacokinetic, and toxicological properties of riparin derivatives

Cited by 43 publications

References 58 publications

In Vitro and In Vivo Studies of Spironolactone as an Antischistosomal Drug Capable of Clinical Repurposing

In Vitro and In Vivo Studies of Spironolactone as an Antischistosomal Drug Capable of Clinical Repurposing

In Vitro and in Vivo Antischistosomal Activities of Chalcones

In-silico studies of Riparin B in the design of drugs: Physicochemical, pharmacokinetic and pharmacodynamic parameters

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