An in vitro method for the chemotherapeutic investigation of anthelminthic potency

Parasitology ◽  
1943 ◽  
Vol 35 (3) ◽  
pp. 89-111 ◽  
Author(s):  
Ernest Baldwin
Keyword(s):  
Quantitative Data ◽  
Technical Skill ◽  
In Vitro Method ◽  
Special Limitation ◽  
Living Material ◽  
New Compounds ◽  
Large Groups ◽  
Selection Of

A method is described for the detection of anthelminthic potency. The procedure does not call for exceptional technical skill, is relatively economical of drugs and living material alike, and is rapid and convenient in application. It has certain limitations such as are inherent in any in vitro method, and a special limitation in that it is not applicable to the study of drugs which act otherwise than on the neuro-muscular mechanisms of nematodes. Within these limitations it responds to compounds of known anthelminthjc efficiency and shows little or no response to compounds known to be devoid of anthelminthie value. Approximate quantitative data can be obtained with its aid, the reactions provoked by a given drug are substantially the same in different individuals, and each test provides a visible record of the influence of the drug under examination.We do not claim that this procedure can in any sense replace experiments upon infested hosts, but must rather be followed up by such experiments when a promising degree of anthelminthie potency has been detected with its aid. We do, however, believe that it has a very real usefulness within the field to which its application is limited. As a preliminary device which allows the selection of promising compounds from large groups of new synthetic products it has already demonstrated its value in tests carried out in this laboratory on a series of about fifty new compounds prepared by Prof. Friedmann.

scholarly journals Structure Activity Relationship of N-Substituted Phenyldihydropyrazolones Against Trypanosoma cruzi Amastigotes

2021 ◽  
Vol 9 ◽  
Author(s):  
Maarten Sijm ◽  
Louis Maes ◽  
Iwan J. P. de Esch ◽  
Guy Caljon ◽  
Geert Jan Sterk ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Drug Effects ◽  
Treatment Compliance ◽  
Treatment Regimens ◽  
Poor Treatment ◽  
Sar Study ◽  
New Compounds ◽  
Relationship Of ◽  
Selection Of

Current drugs for Chagas disease have long treatment regimens with occurrence of adverse drug effects leading to poor treatment compliance. Novel and efficacious medications are therefore highly needed. We previously reported on the discovery of NPD-0227 (2-isopropyl-5-(4-methoxy-3-(pyridin-3-yl)phenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one) as a potent in vitro inhibitor of Trypanosoma cruzi (pIC50 = 6.4) with 100-fold selectivity over human MRC-5 cells. The present work describes a SAR study on the exploration of substituents on the phenylpyrazolone nitrogen. Modifications were either done directly onto this pyrazolone nitrogen or alternatively by introducing a piperidine linker. Attention was pointed toward the selection of substituents with a cLogP preferably below NPD-0227s cLogP of 3.5. Generally the more apolar compounds showed better activities then molecules with cLogPs <2.0. Several new compounds were identified with potencies that are in the same range as NPD-0227 (pIC50 = 6.4) and promising selectivities. While the potency could not be improved, valuable SAR was obtained. Furthermore the introduction of a piperidine linker offers new opportunities for derivatization as valuable novel starting points for future T. cruzi drug discovery.

SNAP Display - an In Vitro Method for the Selection of Protein Binders

2013 ◽  
Vol 19 (30) ◽  
pp. 5421-5428 ◽  
Author(s):  
Gillian Houlihan ◽  
David Lowe ◽  
Florian Hollfelder
Keyword(s):  
In Vitro Method ◽  
Protein Binders ◽  
Selection Of

Clone selection of in vitro horseradish hairy root cultures

Planta Medica ◽  
2015 ◽  
Vol 81 (16) ◽  
Author(s):  
R Bertóti ◽  
Á Alberti ◽  
A Böszörményi ◽  
R Könye ◽  
T Horváth ◽  
...  
Keyword(s):  
Hairy Root ◽  
Hairy Root Cultures ◽  
Root Cultures ◽  
Clone Selection ◽  
Selection Of

A in Vivo Assay for Standardizing Heparin Preparations

1979 ◽  
Vol 41 (03) ◽  
pp. 576-582
Author(s):  
A R Pomeroy
Keyword(s):  
In Vitro Assays ◽  
British Pharmacopoeia ◽  
In Vitro Method ◽  
Standard Preparation ◽  
Reliable Estimation ◽  
Assay Procedure ◽  
Accuracy And Precision ◽  
Heparin Preparation

SummaryThe limitations of currently used in vitro assays of heparin have demonstrated the need for an in vivo method suitable for routine use.The in vivo method which is described in this paper uses, for each heparin preparation, four groups of five mice which are injected intravenously with heparin according to a “2 and 2 dose assay” procedure. The method is relatively rapid, requiring 3 to 4 hours to test five heparin preparations against a standard preparation of heparin. Levels of accuracy and precision acceptable for the requirements of the British Pharmacopoeia are obtained by combining the results of 3 to 4 assays of a heparin preparation.The similarity of results obtained the in vivo method and the in vitro method of the British Pharmacopoeia for heparin preparations of lung and mucosal origin validates this in vivo method and, conversely, demonstrates that the in vitro method of the British Pharmacopoeia gives a reliable estimation of the in vivo activity of heparin.

The Effects of Shock Vancomycin Concentrations on the Formation of Heteroresistance in Staphylococcus aureus

2020 ◽  
Vol 65 (9-10) ◽  
pp. 3-7
Author(s):  
V. V. Gostev ◽  
Yu. V. Sopova ◽  
O. S. Kalinogorskaya ◽  
M. E. Velizhanina ◽  
I. V. Lazareva ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
In Vitro Selection ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
High Concentration ◽  
Short Term ◽  
High Concentrations ◽  
Selection Of ◽  
Selection Of Resistance ◽  
Test Cultures

Glycopeptides are the basis of the treatment of infections caused by MRSA (Methicillin-Resistant Staphylococcus aureus). Previously, it was demonstrated that antibiotic tolerant phenotypes are formed during selection of resistance under the influence of high concentrations of antibiotics. The present study uses a similar in vitro selection model with vancomycin. Clinical isolates of MRSA belonging to genetic lines ST8 and ST239, as well as the MSSA (ATCC29213) strain, were included in the experiment. Test isolates were incubated for five hours in a medium with a high concentration of vancomycin (50 μg/ml). Test cultures were grown on the medium without antibiotic for 18 hours after each exposure. A total of ten exposure cycles were performed. Vancomycin was characterized by bacteriostatic action; the proportion of surviving cells after exposure was 70–100%. After selection, there was a slight increase in the MIC to vancomycin (MIC 2 μg/ml), teicoplanin (MIC 1.5–3 μg/ml) and daptomycin (MIC 0.25–2 μg/ml). According to the results of PAP analysis, all strains showed an increase in the area under curve depending on the concentration of vancomycin after selection, while a heteroresistant phenotype (with PAP/AUC 0.9) was detected in three isolates. All isolates showed walK mutations (T188S, D235N, E261V, V380I, and G223D). Exposure to short-term shock concentrations of vancomycin promotes the formation of heteroresistance in both MRSA and MSSA. Formation of VISA phenotypes is possible during therapy with vancomycin.

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