C0135 In vitro and in silico study of the effect of crocin and safranal on human plasma coagulation

β-citronellol (3,7-dimethyl-6-octen-1-ol) has been exhibiting a number of pharmacological effects that creates interest about its antimicrobial potential, since several substances of the monoterpene class have already demonstrated to possess activity in this profile. In addition, the emergence of fungal species resistant to current pharmacotherapy poses a serious challenge to health systems, making it necessary to search for new effective therapeutic alternatives to deal with this problem. In this study, the antimicrobial profile of β-citronellol was analyzed. The Prediction of Activity Spectra for Substances (PASS) online software was used to study the antimicrobial activity of the β-citronellol molecule by the use of in silico analysis. In contrast, an in vitro antifungal study of this monoterpene was carried out. For this purpose, the Minimum Inhibitory Concentration (MIC) was determined by the microdilution technique in 96-well plates in Saboraud Dextrose Broth/RPMI against sensitive strains of Candida albicans, and this assay was performed in duplicate. In the in silico analysis of the antimicrobial profile, it was revealed that the monoterpene β-citronellol had a diverse antimicrobial bioactivity profile. For the antifungal activity, it presented a percentage value with Pa: 58.4% (predominant) and its MIC of 128 μg/mL, which was equivalent for all strains tested. The in silico study of the β-citronellol molecule allowed us to consider that the monoterpenoid is very likely to be bioactive against agents that cause fungal infections.

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Haemodynamic flow conditions at the initiation of high-shear platelet aggregation: a combined in vitro and cellular in silico study

Interface Focus ◽

10.1098/rsfs.2019.0126 ◽

2020 ◽

Vol 11 (1) ◽

pp. 20190126 ◽

Cited By ~ 1

Author(s):

B. J. M. van Rooij ◽

G. Závodszky ◽

A. G. Hoekstra ◽

D. N. Ku

Keyword(s):

Platelet Aggregation ◽

In Silico ◽

Platelet Rich Plasma ◽

High Shear ◽

Shear Rates ◽

Flow Simulations ◽

In Silico Study ◽

Platelet Aggregates

The influence of the flow environment on platelet aggregation is not fully understood in high-shear thrombosis. The objective of this study is to investigate the role of a high shear rate in initial platelet aggregation. The haemodynamic conditions in a microfluidic device are studied using cell-based blood flow simulations. The results are compared with in vitro platelet aggregation experiments performed with porcine whole blood (WB) and platelet-rich-plasma (PRP). We studied whether the cell-depleted layer in combination with high shear and high platelet flux can account for the distribution of platelet aggregates. High platelet fluxes at the wall were found in silico . In WB, the platelet flux was about twice as high as in PRP. Additionally, initial platelet aggregation and occlusion were observed in vitro in the stenotic region. In PRP, the position of the occlusive thrombus was located more downstream than in WB. Furthermore, the shear rates and stresses in cell-based and continuum simulations were studied. We found that a continuum simulation is a good approximation for PRP. For WB, it cannot predict the correct values near the wall.

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Synthesis, in vitro antifungal activity and in silico study of 3-(1,2,4-triazol-1-yl)flavanones

European Journal of Medicinal Chemistry ◽

10.1016/j.ejmech.2013.06.008 ◽

2013 ◽

Vol 66 ◽

pp. 480-488 ◽

Cited By ~ 22

Author(s):

Saeed Emami ◽

Shahaboddin Shojapour ◽

Mohammad Ali Faramarzi ◽

Nasrin Samadi ◽

Hamid Irannejad

Keyword(s):

Antifungal Activity ◽

In Silico ◽

In Silico Study ◽

In Vitro Antifungal Activity

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Tetroxime: reactivation potency – in vitro and in silico study

RSC Advances ◽

10.1039/c6ra16499d ◽

2017 ◽

Vol 7 (12) ◽

pp. 7041-7045 ◽

Cited By ~ 4

Author(s):

K. Kuca ◽

J. Korabecny ◽

R. Dolezal ◽

E. Nepovimova ◽

O. Soukup ◽

...

Keyword(s):

In Silico ◽

In Silico Study

Tetroxime – a unique bisquaternary compound with four oxime groups.

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Plasma concentration profiles for hepatotoxic pyrrolizidine alkaloid senkirkine in humans extrapolated from rat data sets using a simplified physiologically based pharmacokinetic model

Drug Metabolism Letters ◽

10.2174/1872312801666211220110055 ◽

2021 ◽

Vol 15 ◽

Author(s):

Yusuke Kamiya ◽

Tomonori Miura ◽

Airi Kato ◽

Norie Murayama ◽

Makiko Shimizu ◽

...

Keyword(s):

Plasma Concentration ◽

Human Plasma ◽

In Silico ◽

Pbpk Model ◽

Pyrrolizidine Alkaloid ◽

Water Soluble ◽

Food Plants ◽

Physiologically Based Pharmacokinetic ◽

Physiologically Based

Aim: The main aim of the current study was to obtain forward dosimetry assessments of pyrrolizidine alkaloid senkirkine plasma and liver concentrations by setting up a human physiologically based pharmacokinetic (PBPK) model based on the limited information available. Background: The risks associated with plant-derived pyrrolizidine alkaloids as natural toxins have been assessed. Objective: The pyrrolizidine alkaloid senkirkine was investigated because it was analyzed in a European transcriptomics study of natural hepatotoxins and in a study of the alkaloidal constituents of traditional Japanese food plants Petasites japonicus. The in silico human plasma and liver concentrations of senkirkine were modeled using doses reported for acute-term toxicity in humans. Methods: Using a simplified PBPK model established using rat pharmacokinetic data, forward dosimetry was conducted. Since in vitro rat and human intrinsic hepatic clearances were similar; an allometric scaling approach was applied to rat parameters to create a human PBPK model. Results: After oral administration of 1.0 mg/kg in rats in vivo, water-soluble senkirkine was absorbed and cleared from plasma to two orders of magnitude below the maximum concentration in 8 h. Human in silico senkirkine plasma concentration curves were generated after virtual daily oral administrations of 3.0 mg/kg senkirkine (the dose involved in an acute fatal hepatotoxicity case). A high concentration of senkirkine in the culture medium caused in vitro hepatotoxicity as evidenced by lactate dehydrogenase leakage from human hepatocyte-like HepaRG cells. Conclusion: Higher virtual concentrations of senkirkine in human liver and plasma than those in rat plasma were estimated using the current rat and human PBPK models. Current simulations suggest that if P. japonicus (a water-soluble pyrrolizidine alkaloid-producing plant) is ingested daily as food, hepatotoxic senkirkine could be continuously present in human plasma and liver.

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