5 results on '"Teodori E"'
Search Results
2. Reversal of multidrug resistance by verapamil analogues
- Author
-
Pereira, E., Teodori, E., Dei, S., and Gualtieri, F.
- Published
- 1995
- Full Text
- View/download PDF
3. Carbachol dimers as homobivalent modulators of muscarinic receptors.
- Author
-
Matucci R, Nesi M, Martino MV, Bellucci C, Manetti D, Ciuti E, Mazzolari A, Dei S, Guandalini L, Teodori E, Vistoli G, and Romanelli MN
- Subjects
- Animals, Binding Sites, CHO Cells, Carbachol chemistry, Cricetulus, Dimerization, Guinea Pigs, Humans, Ileum drug effects, Ileum physiology, Male, Mitogen-Activated Protein Kinase 1 metabolism, Mitogen-Activated Protein Kinase 3 metabolism, Molecular Docking Simulation, Muscle Contraction, Muscle, Smooth drug effects, Muscle, Smooth physiology, Phosphorylation, Radioligand Assay, Structure-Activity Relationship, Carbachol analogs & derivatives, Carbachol pharmacology, Muscarinic Antagonists pharmacology
- Abstract
A series of homodimers of the well-known cholinergic agonist carbachol have been synthesized, showing the two agonist units symmetrically connected through a methylene chain of variable length. The new compounds have been tested on the five cloned muscarinic receptors (hM1-5) expressed in CHO cells by means of equilibrium binding studies, showing an increase in affinity by rising the number of methylene units up to 7 and 9. Functional experiments on guinea-pig ileum and assessment of ERK1/2 phosphorylation on hM1, hM2 and hM3 on CHO cells have shown that the new compounds are endowed with muscarinic antagonistic properties. Kinetic binding studies have revealed that some of the tested compounds are able to slow the rate of dissociation of NMS, suggesting a bitopic behavior. Docking simulations, performed on the hM1 and hM2 receptors, give a sound rationalization of the experimental data revealing how these compounds are able to interact with both orthosteric and allosteric binding sites depending on the length of their connecting chain., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
4. N,N-bis(cyclohexanol)amine aryl esters inhibit P-glycoprotein as transport substrates.
- Author
-
Neri A, Frosini M, Valoti M, Cacace MG, Teodori E, and Sgaragli G
- Subjects
- ATP Binding Cassette Transporter, Subfamily B, ATP Binding Cassette Transporter, Subfamily B, Member 1 genetics, ATP Binding Cassette Transporter, Subfamily B, Member 1 metabolism, Adenosine Triphosphatases metabolism, Animals, Cell Line, Tumor, Cell Membrane enzymology, Drug Resistance, Neoplasm drug effects, Gene Expression Regulation drug effects, Humans, Mice, ATP Binding Cassette Transporter, Subfamily B, Member 1 antagonists & inhibitors, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology
- Abstract
P-Glycoprotein (Pgp) inhibition by three sets of four isomers of N,N-bis(cyclohexanol)amine aryl esters was assessed on rhodamine 123 (R123) efflux in human MDR1-gene transfected mouse T-lymphoma L5178 cells and on Sf9 ATPase activity. The most active compounds inhibited Pgp with IC(50) values much lower than those of either cyclosporin A (CSA) or GF120918. As to R123 efflux inhibition, the role of the bond present in the second aryl moiety appeared important since the triple bond derivatives (3a-d) were the most powerful as compared to the double bond (2a-d) and the single bond (1a-d) counterparts. Concentration-inhibition curves of 2c and 3d exhibited a biphasic behaviour suggesting the existence of two binding sites in the recognition domain of Pgp. Persistence of inhibition by these compounds resulted to be intermediate between that caused by CSA and GF120918. R123 exhibited positive interaction with CSA, 1d, 1c, 2d, 2c and 3c, the concentration-inhibition curves being shifted leftward when R123 concentration was increased, while it exhibited negative interaction with 3d and no effect with GF120918. Sf9 ATPase activity was stimulated in an increasing order of potency by 2c, 3c, 2d, CSA, epirubicin and 3d. In a decreasing order of potency 3d, 2c, GF120918, CSA, 2d and 3c inhibited at sub-nanomolar concentrations epirubicin-stimulated ATPase activity. In conclusion, isomeric geometry and restriction of molecular flexibility of N,N-bis(cyclohexanol)amine aryl esters were crucial for their presentation to and inhibition of Pgp as transport substrates, R123 and epirubicin cooperating with them to this inhibition., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
5. Muscarinic subtype affinity and functional activity profile of 1-methyl-2-(2-methyl-1,3-dioxolan-4-yl)pyrrolidine and 1-methyl-2-(2-methyl-1,3-oxathiolan-5-yl)pyrrolidine derivatives.
- Author
-
Dei S, Angeli P, Bellucci C, Buccioni M, Gualtieri F, Marucci G, Manetti D, Matucci R, Romanelli MN, Scapecchi S, and Teodori E
- Subjects
- Animals, CHO Cells, Cricetinae, Guinea Pigs, Humans, In Vitro Techniques, Male, Muscarinic Agonists chemistry, Muscarinic Antagonists chemistry, Protein Binding drug effects, Protein Binding physiology, Protein Isoforms agonists, Protein Isoforms antagonists & inhibitors, Protein Isoforms physiology, Pyrrolidines chemistry, Rabbits, Structure-Activity Relationship, Muscarinic Agonists pharmacology, Muscarinic Antagonists pharmacology, Pyrrolidines pharmacology, Receptors, Muscarinic physiology
- Abstract
Starting from two previously studied muscarinic full agonists, characterized by a 1,3-dioxolane ((+)-1) and a 1,3-oxathiolane ((+)-2) cycle, two new series of muscarinic ligands were designed, obtained by the steric complication of the parent compounds produced by freezing the aminoalkyl chain into a pyrrolidine ring. Both tertiary amines and the corresponding iodomethyl derivatives were synthesised and studied, and several compounds of the series which behaved as muscarinic agonists have been selected, on the basis of preliminary binding experiments on rat cortex homogenates, for the present work. Results are presented obtained from testing the affinity of the selected compounds against cloned human muscarinic receptors expressed in CHO cells, in order to evaluate subtype selectivity. Their functional activity on classical models of M1-M4 receptors, in guinea pig and rabbit tissues is also reported. With respect to parent compounds, the new molecules present some selectivity toward hm2 receptors; fair M2 selectivity is also evident in functional studies, where these compounds behave as partial agonists. Among the other compounds of the series (2S, 4'R, 2'S)-1,1-dimethyl-2-(2-methyl-1,3-dioxolan-4-yl)pyrrolidinium iodide (-)-3 and (2R, 5'S, 2'S)-1-methyl-2-(2-methyl-1,3-oxathiolan-5-yl)pyrrolidine (+)-5 present a promising pharmacological profile. Compound (-)-3 shows modest hm2 selectivity in binding experiments but a clearcut M2 selectivity in functional tests, where it behaves as a weak antagonist on M1 and M4 subtypes, as a weak full agonist on the M3 subtype and as a potent partial agonist on M2 subtype. Tertiary amine (+)-5 presents a quite similar profile but appears more interesting since, lacking a permanent charge on the nitrogen atom, it may represent an interesting tool to study CNS muscarinic receptors. Our results confirm that sterical complication of parent compounds (+)-1 and (+)-2 produces more selective muscarinic agonists.
- Published
- 2005
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.