Sanz F

References (2)

Title : Anchor-GRIND: filling the gap between standard 3D QSAR and the GRid-INdependent descriptors - Fontaine_2005_J.Med.Chem_48_2687
Author(s) : Fontaine F , Pastor M , Zamora I , Sanz F
Ref : Journal of Medicinal Chemistry , 48 :2687 , 2005
Abstract : The aim of this work is to present the anchor-GRIND methodology. Anchor-GRIND efficiently combines a priori chemical and biological knowledge about the studied compounds with alignment-independent molecular descriptors derived from molecular interaction fields. Such descriptors are particularly useful for series of ligands sharing a common scaffold but with very diverse substituents. The method uses a specific position of the molecular structure (the "anchor point") to compare the spatial distribution of the molecular interaction fields of the substituents. The descriptors produced are more detailed and specific than the original GRIND while still avoiding the bias introduced by the alignment. Three data sets have been studied to demonstrate the usefulness of the anchor-GRIND methodology for 3D-QSAR modeling. The two first data sets respectively include congeneric series of the hepatitis C virus NS3 protease and of the acetylcholinesterase inhibitors. The third data set discriminates between factor Xa inhibitors of high and low affinity. In all the series presented, the models obtained with the anchor-GRIND are statistically sound and easy to interpret.
ESTHER : Fontaine_2005_J.Med.Chem_48_2687
PubMedSearch : Fontaine_2005_J.Med.Chem_48_2687
PubMedID: 15801859

Title : Acute toxicity of several organophosphorous insecticides and protection by cholinergic antagonists and 2-PAM on Artemia salina larvae - Sanchez-Fortun_1996_Arch.Environ.Contam.Toxicol_31_391
Author(s) : Sanchez-Fortun S , Sanz F , Barahona MV
Ref : Archives of Environmental Contamination & Toxicology , 31 :391 , 1996
Abstract : The acute toxicity of chlorpyrifos, methylchlorpyrifos, parathion and methylparathion to three age classes of Artemia salina was determined. In general, A. salina 24-h old was less sensitive to these organophosphorous insecticides (OPI) than A. salina 48-h old and A. salina 48-h old was significantly more tolerant than A. salina 72-h old, in contrast, chlorpyrifos was equally toxic to A. salina 48- and 72-h old. There were some differences among the three age classes of A. salina in the relative order of toxicity of OPI tested. The rank order of toxicity to A. salina 48-h old was methylparathion < parathion < methyl-chlorpyrifos < chlorpyrifos, while to A. salina 24- and 72-h old it was methylparathion = parathion < methyl-chlorpyrifos < chlorpyrifos. The protective effect of the cholinergic antagonists atropine, hexamethonium, pirenzepine and 11-(2-((diethyl-amino)methyl)-1-piperidinylacetyl)-5, 11-dihydro-6H-pyrido(2,3-b)-(1,4)-benzodiazepine-6-one (AF-DX 116) and a cholinesterase-reactivating oxime 2-pyridine aldoxime methochloride (2-PAM) on the mortality due to four selected OPI in Artemia salina 24-h old was investigated. The lethal action of OPI tested was completely prevented by pretreatment of Artemia salina 24-h old with 2-PAM (10(-5) M) and atropine (10(-4 )M). However no concentration of hexamethonium, pirenzepine or AF-DX 116 protected 100% of the animals poisoned by LC84 of the OPI selected, maximum protection obtained was 71 to 88%. In contrast, the maximum inhibition of mortality obtained with AF-DX 116 pretreatment was about 55% because this compound was used at concentrations which were non toxic to control Artemia salina. Atropine, hexamethonium, pirenzepine, AF-DX 116 and 2-PAM afforded 50 % protection (IC50) of Artemia salina against mortality by LC84 of the OPI selected at concentrations in the range of 6.62x10(-7)-1.6x10(-6) M, 2. 38x10(-4)-2.05x10(-3)M, 8.91x10(-7)-1.24x10(-6) M, 9.66x10(-8)-1. 34x10(-7 )M, and 1.95x10(-8)-2.73x10(-8 )M, respectively. Pretreatment of atropine plus 2-PAM to determine whether this combination afforded greater inhibition of the lethality induced by four OPI tested than pretreatment with either atropine or 2-PAM alone was investigated. Atropine (10(-5) M) in combination with 2-PAM (10(-7 )M) inhibited completely the acute toxicity of all OPI tested, while the pretreatment with atropine (10(-6) M) plus 2-PAM at the same concentration gave a inhibition of mortality (about 62%) significantly greater than each antagonist alone (about 14 and 46%, respectively).
ESTHER : Sanchez-Fortun_1996_Arch.Environ.Contam.Toxicol_31_391
PubMedSearch : Sanchez-Fortun_1996_Arch.Environ.Contam.Toxicol_31_391
PubMedID: 8854833