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Cytotoxicity of acetylcholinesterase reactivators evaluated in vitro and its relation to their structure
- Source :
- Drug and Chemical Toxicology. 42:252-256
- Publication Year :
- 2018
- Publisher :
- Informa UK Limited, 2018.
-
Abstract
- The development of acetylcholinesterase reactivators, i.e., antidotes against organophosphorus poisoning, is an important goal of defense research. The aim of this study was to compare cytotoxicity and chemical structure of five currently available oximes (pralidoxime, trimedoxime, obidoxime, methoxime, and asoxime) together with four perspective oximes from K-series (K027, K074, K075, and K203). The cytotoxicity of tested substances was measured using two methods - colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay and impedance based real-time cytotoxicity assay - in three different cell lines (HepG2, ACHN, and NHLF). Toxicity was subsequently expressed as toxicological index IC50. The tested compounds showed different cytotoxicity ranging from 0.92 to 40.06 mM. In HepG2 cells, K027 was the least and asoxime was the most toxic reactivator. In ACHN and NHLF cell lines, trimedoxime was the compound with the lowest adverse effects, whereas the highest toxicity was found in methoxime-treated cells. The results show that at least five structural features affect the reactivators' toxicity such as the number of oxime groups in the molecule, their position on pyridinium ring, the length of carbon linker, and the oxygen substitution or insertion of the double bond into the connection chain. Newly synthetized oximes with IC50 ≥ 1 mM evaluated in this three cell lines model might appear suitable for further testing.
- Subjects :
- Obidoxime
Cholinesterase Reactivators
Pralidoxime
Cell Survival
Health, Toxicology and Mutagenesis
Chemical structure
Drug Evaluation, Preclinical
010501 environmental sciences
Animal Testing Alternatives
Toxicology
01 natural sciences
Lethal Dose 50
Inhibitory Concentration 50
Structure-Activity Relationship
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Oximes
medicine
Humans
Trimedoxime
Cytotoxicity
0105 earth and related environmental sciences
Pharmacology
Chemical Health and Safety
Molecular Structure
Public Health, Environmental and Occupational Health
Hep G2 Cells
General Medicine
Fibroblasts
Oxime
Acetylcholinesterase
Combinatorial chemistry
chemistry
Toxicity
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 15256014 and 01480545
- Volume :
- 42
- Database :
- OpenAIRE
- Journal :
- Drug and Chemical Toxicology
- Accession number :
- edsair.doi.dedup.....f696141ec2a025acb95c0e7f21b3d57b