ABSTRACT
Based upon synthetic and biochemical results, a novel and potent tacrine analogue and heterobivalent analogues of tacrine, were designed. The role played by the amino groups of homo- and heterobivalent ligands in the interaction with the peripheral and catalytic sites of AChE and BuChE were investigated. The syntheses of these materials together with the results of AChE/BuChE inhibition assays are detailed.
Subject(s)
Acetylcholinesterase/metabolism , Butyrylcholinesterase/metabolism , Tacrine/metabolism , Acetylcholinesterase/chemistry , Butyrylcholinesterase/chemistry , Catalytic Domain , Ligands , Tacrine/chemistryABSTRACT
A large series of 2-aryl(heteroaryl)-2,5-dihydropyrazolo[4,3-c]quinolin-3(3H)-ones (PQ, 106 compounds), carrying appropriate substituents at the quinoline and N2-phenyl rings, were designed, prepared and tested as central benzodiazepine receptor ligands. Compounds with an affinity significantly higher than the parent compound CGS-8216 were obtained, the most active ligand showing a pIC50 = 10.35. Hansch and comparative molecular field analyses gave coherent results suggesting the main structural requirements of high receptor binding affinity. The possible formation of a three-centred hydrogen bond (HB) at the HB donor site H2, as a key interaction for high receptor binding affinity, was assessed by the calculation and comparison of the molecular electrostatic potentials of a series of selected ligands.
Subject(s)
Quantitative Structure-Activity Relationship , Receptors, GABA-A/metabolism , Animals , Binding, Competitive , Cerebral Cortex/metabolism , GABA Agonists/chemical synthesis , GABA Agonists/chemistry , GABA Agonists/metabolism , GABA Antagonists/chemical synthesis , GABA Antagonists/chemistry , GABA Antagonists/metabolism , Inhibitory Concentration 50 , Ligands , Magnetic Resonance Spectroscopy , Male , Models, Molecular , Protein Binding , Pyrazoles/metabolism , Quinolones/chemical synthesis , Quinolones/chemistry , Quinolones/metabolism , Rats , Rats, Sprague-Dawley , Receptors, GABA-A/chemistry , Static ElectricityABSTRACT
The synthesis of a series of 1,2,4-triazolo[4,3-a]quinoline derivatives is described; their structures were assigned by 1H NMR and analytical data. The new compounds were tested in vivo for their antiinflammatory and analgesic activities, as well as for their ulcerogenic action. Some of the tested triazoles showed an analgesic activity in the acetic acid writhing test and antiinflammatory properties on carrageenan paw edema assay.
Subject(s)
Analgesics/chemical synthesis , Anti-Inflammatory Agents/chemical synthesis , Isoquinolines/pharmacology , Triazoles/pharmacology , Analgesics/pharmacology , Analgesics/toxicity , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/toxicity , Edema/drug therapy , Edema/prevention & control , Female , Isoquinolines/chemical synthesis , Isoquinolines/toxicity , Magnetic Resonance Spectroscopy , Male , Mice , Molecular Structure , Pain/drug therapy , Pain/prevention & control , Structure-Activity Relationship , Triazoles/chemical synthesis , Triazoles/toxicityABSTRACT
A number of pyruvic acid and methylpyruvate alpha-(N)-heterocyclic hydrazones has been synthesized. Bis-heterocyclic hydrazones were obtained from reaction with pyruvic carboxaldehyde. Some complexes of Ni(II) were prepared and characterized as neutral complexes. All these compounds have been evaluated for cytotoxicity against P388 and HL-60 leukemia.
Subject(s)
Antineoplastic Agents/chemical synthesis , Chelating Agents/chemical synthesis , Hydrazones/chemical synthesis , Animals , Antineoplastic Agents/pharmacology , Chelating Agents/pharmacology , Drug Screening Assays, Antitumor , HL-60 Cells , Humans , Hydrazones/pharmacology , Leukemia P388/drug therapy , Ligands , Magnetic Resonance Spectroscopy , Mice , Spectrophotometry, Infrared , Tumor Cells, CulturedABSTRACT
Several 1-[quinolyl(4)]-1,2,3-triazoles were synthesized by 1,3-dipolar cycloaddition of 4-azidoquinolines with activated methylene compounds. The synthesized compounds, tested for antiinflammatory and analgesic activities, resulted moderately active as antiinflammatories, but with a very interesting analgesic activity, sometimes higher than that of indomethacin, used as reference drug. Some of the triazole derivatives were evaluated also as antimicrobial, but none of them exhibited activity.
Subject(s)
Analgesics/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Triazoles/chemical synthesis , Analgesics/pharmacology , Animals , Anti-Infective Agents/chemical synthesis , Anti-Infective Agents/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Male , Rats , Rats, Wistar , Structure-Activity Relationship , Triazoles/pharmacologyABSTRACT
The synthesis of new 1-[quinolyl(4)]-1,2,3-triazoles is reported. These have been obtained by reacting 4-azidoquinolines with ethyl p-nitrobenzoylacetate. The synthesized compounds, tested for antiinflammatory and analgesic activities, results moderately active as antiinflammatories, but with a very interesting analgesic activity, sometimes higher than that of indomethacin, used as reference drug.
