QSTR study for two series of novel succinimide derivatives - evaluation of in silico minnow toxicity
Fathead minnow (Pimephales promelas) test are applied for the evaluation of aqueous toxicity of xenobiotics. The environmental hazardous effect of newly synthesized compounds and drug candidates can also be evaluated in silico since many quantitative structure–toxicity relationship (QSTR) models are...
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| Dokumentumtípus: | Könyv része |
| Megjelent: |
University of Szeged
Szeged
2024
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| Sorozat: | Proceedings of the International Symposium on Analytical and Environmental Problems
30 |
| Kulcsszavak: | Gyógyszerkémia, Toxikológia - értékelés - módszer, Környezetkémia |
| Tárgyszavak: | |
| Online Access: | http://acta.bibl.u-szeged.hu/85696 |
| Tartalmi kivonat: | Fathead minnow (Pimephales promelas) test are applied for the evaluation of aqueous toxicity of xenobiotics. The environmental hazardous effect of newly synthesized compounds and drug candidates can also be evaluated in silico since many quantitative structure–toxicity relationship (QSTR) models are recognized as less expensive alternatives. In this study two series of succinimide derivatives were assessed for Minnow toxicity in silico by applying pkCSM online tool. Minnow toxicity was quantified as logLC50 (mM) value for all analysed compounds whereas LC50 is the concentration of a molecules necessary to cause the death of 50% of the Flathead Minnows. Physicochemical descriptors of the analysed compounds such as molar weight, molar refractivity and polar surface area were determined by the SwissADME online platform, while the lipophilicity (logD, logP) and aqueous solubility (logS) were quantified by the application of PreADMET online tool. The predicted toxicity was correlated to literature experimentally obtained lipophilicity for the observed molecules. The minnow logLC50 for all twenty-four succinimide derivatives was above -0.3 indicating very low acute toxicity. The compounds of the series C in comparison to the series D compounds had statistically significant higher minnow logLC50 (p=0.007) indicating lower toxic potential. The predicted toxicity was negatively correlated with molar weight (p=1.45×10-4 ) and molar refractivity (p=8.21×10-4 respectively. Minnow logLC50 values were negatively associated with both in silico (logD values on pH 7.4 and logP, respectively, p<0.001 for both relations), and experimentally quantified lipophilicity (RM 0 values with acetone-water mixture, p<0.001 and acetonitrile-water as mobile phase p<0.001, respectively). Aqueous solubility was positively associated with minnow logLC50 (p<0.001) indicating lower toxicity for more soluble compounds. Despite the higher aquatic solubility, the compounds of the series C are recognized as less toxic molecules in comparison to the compounds of the series D. |
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| Terjedelem/Fizikai jellemzők: | 156-160 |
| ISBN: | 978-963-688-009-5 |