Nine bispyridinium oximes containing two pyridinium rings linked by dimethylether were synthesised. Each compound had on one of the pyridinium rings a hydroxyiminomethyl group in position 2 or 4, while the other ring was unsubstituted or had a methyl or a hydroxyiminomethyl group in position 2 or 4. The reactivating potency and therapeutic effect of the oximes were tested on two organophosphates: O,O-dimethyl-2,2-dichlorovinylphosphate (DDVP) and O-ethyl-S-(2-diisopropylaminoethyl)-methylphosphonothioate (VX). The reactivation was measured on human erythrocyte acetylcholinesterase and the therapeutic effect was evaluated on male albino rats. The oximes with a hydroxyiminomethyl group in position 4 in the pyridinium ring were good reactivators of both phosphorylated and phosphonylated acetylcholinesterase. They were also very effective given together with atropine against VX and DDVP poisoning. The compounds are almost as effective as PAM-2, but PAM-2 is less toxic.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/BF00296900 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Disentangling the formation, mechanism, and evolvement of the covalent methanesulfonyl fluoride acetylcholinesterase adduct: Insights into an aged-like inactive complex susceptible to reactivation by a combination of nucleophiles.
Protein Sci
May 2024
Trieste Outstation, Area Science Park-Basovizza, Institute of Crystallography, National Research Council, Trieste, Italy.
Chemical warfare nerve agents and pesticides, known as organophosphorus compounds inactivate cholinesterases (ChEs) by phosphorylating the serine hydroxyl group located at the active site of ChEs. Over the course of time, phosphorylation is followed by loss of an organophosphate-leaving group and the bond with ChEs becomes irreversible, a process known as aging. Differently, structurally related irreversible catalytic poisons bearing sulfur instead of phosphorus convert ChEs in its aged form only by covalently binding to the key catalytic serine.
View Article and Find Full Text PDFDiscovery of Novel Hydroxyimine-Tethered Benzenesulfonamides as Potential Human Carbonic Anhydrase IX/XII Inhibitors.
ACS Med Chem Lett
June 2023
Medicinal Chemistry and Drug Discovery Research Laboratory, Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi-110025, India.
To discover novel carbonic anhydrase (CA, EC 4.2.1.
View Article and Find Full Text PDFIn Situ Ligand Formation in the Synthetic Processes from Mononuclear Dy(III) Compounds to Binuclear Dy(III) Compounds: Synthesis, Structure, Magnetic Behavior, and Theoretical Analysis.
Inorg Chem
January 2021
Dalian National Laboratory for Clean Energy and State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, P. R. China.
Guided by the self-assembled process and mechanism, the strategy of in situ Schiff base reaction would be capable of bringing a feasible method to construct and synthesize lanthanide compounds with distinct structures and magnetic properties. A mononuclear Dy(III) compound was synthesized through a multidentate Schiff base ligand and a chelating β-diketonate ligand, which was named as [Dy(L)(bppd)]·CHOH [; HL = ,'-bis(2-hydroxy-5-methyl-3-formylbenzyl)-,'-bis(pyridin-2-ylmethyl)ethylenediamine and bppd = 3-bis(pyridin-2-yl)propane-1,3-dione]. Furthermore, a new binuclear Dy(III) compound, [Dy(HLox)(bppd)]·8CHOH [; HLox = ,'-bis[2-hydroxy-5-methyl-3-(hydroxyiminomethyl)benzyl]-,'-bis(pyridin-2-ylmethyl)ethylenediamine], was obtained via an in situ synthetic process.
View Article and Find Full Text PDFSubstitution at the indole 3 position yields highly potent indolecombretastatins against human tumor cells.
Eur J Med Chem
October 2018
Laboratorio de Química Orgánica y Farmacéutica, Departamento de Ciencias Farmacéuticas, Universidad de Salamanca, Campus Miguel de Unamuno, E-37007, Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Facultad de Farmacia, Universidad de Salamanca, Campus Miguel de Unamuno, E-37007, Salamanca, Spain; Centro de Investigación de Enfermedades Tropicales de la Universidad de Salamanca (CIETUS). Facultad de Farmacia, Universidad de Salamanca, Campus Miguel de Unamuno, E-37007, Salamanca, Spain. Electronic address:
Resistance to combretastatin A-4 is mediated by metabolic modification of the phenolic hydroxyl and ether groups of the 3-hydroxy-4-methoxyphenyl (B ring). Replacement of the B ring of combretastatin A-4 by a N-methyl-5-indolyl reduces tubulin polymerization inhibition (TPI) and cytotoxicity against human cancer cell lines but cyano, methoxycarbonyl, formyl, and hydroxyiminomethyl substitutions at the indole 3-position restores potent TPI and cytotoxicity against sensitive human cancer cell lines. These highly potent substituted derivatives displayed low nanomolar cytotoxicity against several human cancer cell lines due to tubulin inhibition, as shown by cell cycle analysis, confocal microscopy, and tubulin polymerization inhibitory activity studies, and promoted cell killing mediated by caspase-3 activation.
View Article and Find Full Text PDFComputational elucidation of the reaction mechanism for synthesis of pyrrolidinedione derivatives Nef-type rearrangement - cyclization reaction.
RSC Adv
January 2018
Faculty of Chemistry and Pharmacy, University of Sofia 1, James Bourchier Blvd 1126 Sofia Bulgaria
This paper reports a quantum chemical study of all stages of a one-pot synthesis of pyrrolidinedione derivatives from nitromethane and coumarin, which includes Michael addition, migration of an oxygen atom (Nef-type rearrangement), and cyclization to a pyrrolidine ring. The energy barrier of deprotonated nitromethane addition to coumarin is 21.7 kJ mol, while the barrier of proton transfer from the methylene to the nitro group in the nitromethyl group is notably higher, 197.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!