Browsing by Author "de los Rios, C"
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- Novel tacrine derivatives that block neuronal calcium channelsPublication . de los Rios, C; Marco, JL; Carreiras, MDC; Chinchon, PM; Garcia, AG; Villarroya, MA new series of tacrine (9-amino-1,2,3,4-tetrahydroacridine) derivatives were synthesized and their effects on Ca-45 (2+) entry into bovine adrenal chromaffin cells stimulated with dimethylphenylpiperazinium (DMPP) or K+, studied. At 3 PM, compound 1 did not affect Ca-45(2+) uptake evoked by DMPP. Compounds 14, 15 and 17 inhibited the effects of DMPP by 30%. Compounds 3, 9 and tacrine blocked the DMPP signal by about 50%. Compounds 5 and 12 were the most potent blockers of DMPP-stimulated (45)Ca2(+) entry (90%); the rest of the compounds inhibited the effects of DMPP by 70-80%. Compounds 1, 3, 4, 8, 10, If, 13, 16, 17 and tacrine inhibited Ca-45(2+) Uptake induced by K+ about 20%. Compounds 6. 14 and 15 inhibited the K+ effects by 10% or less. Compounds 7, 9, 12 and 18 blocked the K+ signal by 30% and, finally, compounds 2 and 5 inhibited the K+-induced Ca-45(2+) entry by 50%, None of the new compounds was as effective as diltiazem (IC50 0.03 muM) in causing relaxation of the rat aorta precontracted with 35 mM K+; the most potent was compound 7(IC50 = 0.3 muM). Compounds 5, 6, 8, 9, 10 and 13 had IC(50)s around 10 muM and compounds 3, 4, 11 and 12 around 20 muM. Blockade of Ca2+ entry through neuronal voltage-dependent Ca2+ channels, without concomitant blockade of vascular Ca2+ channels, suggests that some of these compounds might exhibit neuroprotectant effects but not undesirable hemodynamic effects. (C) 2002 Elsevier Science Ltd. All rights reserved.
- Synthesis and acetylcholinesterase/butyrylcholin-esterase inhibition activity of 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro(and thieno)[2,3-b]quinolines, and 4-amino-5,6,7,8,9-pentahydro-2,3-diphenylcyclohepta[e]furo(and thieno)-[2,3-b]pyridinePublication . Marco, JL; de los Rios, C; Carreiras, MC; Banos, JE; Badia, A; Vivas, NMThe acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition activities of a series of 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (10-12)/4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (14) and 4-amino-5,6,7,8,9-pentahydro-2,3-diphenylcyclohepta[e]furo[2,3-b]pyridine (13)/4amino-5,6,7,8,9-pentahydro-2,3-phenylcyclohepta[e]thieno[2,3-b]pyridine (15) are described. These compounds are tacrine (THA) analogues which have been prepared either from readily available 2-amino-3-cyano-4,5-diarylfurans (16-18) or from 2-amino-3-cyano-4,5-diphenylthiophene (19), via Friedlander condensation with cyclohexanone or cycloheptanone. These compounds are competitive inhibitors for acetylcholinesterase, the more potent being compound (13) which is threefold less active than tacrine. The butyrylcholinesterase inhibition activity is significant only in compounds 10 and 13, which are ten-fold less active than tacrine. It is found that the products 11 and 12 strongly inhibit acetylcholinesterase, and show excellent selectivity regarding butyrylcholinesterase.
- Synthesis and acetylcholinesterase/butyrylcholinesterase inhibition activity of new tacrine-like analoguesPublication . Marco, JL; de los Rios, C; Carreiras, MC; Banos, JE; Badia, A; Vivas, NMThe synthesis and preliminary results for acetylcholinesterase and butyrylcholinesterase inhibition activity of a series of pyrano[2,3-b]quinolines (2, 3) and benzonaphthyridines (5, 6) derivatives are described. These molecules are tacrine-like analogues which have been prepared from readily available polyfunctionalized ethyl [6-amino-5-cyano-4H-pyrans and 6-amino-5-cyanopyridine s]-3-carboxylates via Friedlander condensation with selected ketone s. These compounds showed moderate acetylcholinesterase inhibition activity, the more potent (2e, 5b) being 6 times less active than tacrine. The butyrylcholinesterase activity of some of these molecules is also discussed. (C) 2001 Elsevier Science Ltd. All rights reserved.
- Synthesis and Biological Assessment of Furoquinolines, Pyrroloquinolines and Analogues Towards Cholinesterases and Monoamine Oxidases A and BPublication . Martins, C; Carreiras, MC; Mendes, E; de los Rios, C; Léon, R; Ramsay, R; Marco-Contelles, J
- Synthesis, biological evaluation and molecular modelling of diversely functionalized heterocyclic derivatives as inhibitors of acetylcholinesterase/butyrylcholinesterase and modulators of Ca2+ channels and nicotinic receptorsPublication . Marco, JL; de los Rios, C; Garcia, AG; Villarroya, M; Carreiras, MC; Martins, C; Eleuterio, A; Morreale, A; Orozco, M; Luque, FJThe synthesis and the biological activity of compounds 5-40 as inhibitors of acetyleholinesterase (AChE) and butyrylcholinesterase (BuChE), as well as modulators of voltage-dependent Ca2+ channels and nicotinic receptors, are described. These molecules are tacrine analogues, which have been prepared from polyfunctionalized 6-amino-5-cyano-4H-pyrans, 6-amino-5-cyano-pyridines and 5-amino-2-aryl-3-cyano-1,3-oxazoles via Friedlander reaction with selected cycloalkanones. These compounds are moderate acetylcholinesterase and butyrylcholinesterase inhibitors, the BuChE/AChE selectivity of the most active molecules ranges from 10.0 (compound 29) to 76.9 (compound 16). Interestingly, the 'oxazolo-tacrine' derivatives are devoid of any activity. All compounds showed an important inhibitory effect on the nicotinic acetylcholine receptor. Most of them also blocked L-type Ca2+ channels, and three of them, 64, 19 and 67, the non-L type of Ca2+ channels. Molecular modelling studies suggest that these compounds might bind at the peripheral binding site of AChE, which opens the possibility to design inhibitors able to bind at both, the catalytic and peripheral binding sites of the enzyme. (C) 2004 Elsevier Ltd. All rights reserved.