Jose A. Fontenla

• PhD
• Head of Research Team at University of Santiago de Compostela

Gamma-decanolactone (GD) is a monoterpene compound with anticonvulsant, antiparkinsonian, and neuroprotective effects in preclinical trials. This study aimed to evaluate the toxicity and antioxidant profile of GD in silico and in the Caenorhabditis elegans (C. elegans) experimental model. The C. elegans was used to determine the median lethal conce...

Psychiatric and neurological disorders affect millions of people worldwide. Currently available treatments may help to improve symptoms, but they cannot cure the diseases. Therefore, there is an urgent need for potent and safe therapeutic solutions. 8-Amide and 8-carbamatecoumarins were synthetized and evaluated as human monoamine oxidase A and B (...

Treatment of Parkinson's disease (PD) includes the use of monoamine oxidase-B (MAO-B) inhibitor drugs. In this work we have evaluated the possible gamma-decanolactone (GD) effect in vitro to inhibit the A and B isoforms of human monoamine oxidase (hMAO) enzyme and their citotoxicity in human hepatoma cell line (HepG2). Also, binding studies to A1,...

The 3-pyridazinylcoumarin scaffold was previously reported as an efficient core for the discovery of reversible and selective inhibitors of MAO-B, a validated drug target for PD therapy which also plays an important role in the AD progress. Looking for its structural optimization, novel compounds of hybrid structure coumarin-pyridazine, differing i...

This study aimed to investigate the possible gamma-decanolactone mechanisms of action in the GABAergic and adenosine systems using the aminophylline-induced acute crisis model and the pentylenetetrazole-induced kindling model. In the acute model, male mice received administration of bicuculline (GABAA receptor antagonist), 8-cyclopentyl-1,3-dipropy...

Monoamine oxidase B (MAO-B) inhibitors are still receiving great attention as promising therapeutic agents for central nervous system disorders. This study explores, for the first time, the potential of 3-thiophenylcoumarins as in vitro and in vivo agents against Parkinsońs disease. Twelve compounds were synthesized via Perkin-Oglialoro reaction, a...

The acute phase of depression is often accompanied by anxiety, irritability and insomnia. As a result, the concomitant use of an anxiolytic agent with an antidepressant is often necessary. At the present there are drugs very effective in treating depression, however, much of them have more side effects, so they usually are not the first drugs used...

Monoamine oxidase (MAO) is an enzyme responsible for metabolism of monoamine neurotransmitters which plays an important role in the brain development and function. This enzyme exists as two isoforms, and it has been demonstrated that MAO-B activity, but not MAO-A activity, increases with aging. MAO inhibitors show a clinical value because besides t...

One of the biggest challenges in the modern medicine and the food industry is to provide chemical agents that, incorporated in the foods, could have some pharmacological properties, but mainly that can protect and preserve our health from oxidative stress, and could be used in clinical treatments against some chronic diseases with minor side effect...

Sida acuta Burm. f., Malvaceae, is regarded as astringent, tonic and useful in treating urinary diseases and blood disorders, bile, liver and as treatment for nervous diseases. Different methods were developed: sodium pentobarbital-induced sleeping time, anxiolytic activity, test for muscle-effects, pentylenetetrazole (PTZ)-induced seizures, effect...

Anxiety is one of the behavior disorders that has been studied more together with depression in the world, and that has enormous interference in the mental health of the affected patients. The states of panic and phobia are a part of the psychological characteristics that some drugs have tried to control though with varied side effects that are pro...

Background: Due to the complex etiology of neurodegenerative diseases, there is growing interest in multitarget drugs. In this study we synthesized and evaluated a new series of compounds, with benzo[f]coumarin structure, as potential inhibitors of MAO-A, MAO-B, AChE and BuChE. Results: In vitro studies show that most of the studied compounds in...

In this study we evaluate the in vivo antidepressant effect of a natural phenolic compound, trans-resveratrol, and a synthetic derivative from Menispermum dauricum DC (Menispermaceae) 5-methoxy-7H-dibenzo[de,h]quinolin-7-one known as 5-methoxyoxoisoaporphine (OXO 4). The antidepressant-like effect of trans-resveratrol and OXO 4 were evaluated throu...

A series of (coumarin-3-yl)carbamates was synthesized and evaluated in vitro as monoamine oxidase (MAO-A and MAO-B) inhibitors. Most of the new compounds selectively inhibited MAO-B isoenzyme with IC50 values in the micro or nanoMolar ranges. Since these compounds must achieve the brain cells, theoretical evaluation of ADME properties were also car...

Oxoisoaporphine nanocapsules for treating depression are disclosed. Nanocapsule systems are described that incorporate oxoisoaporphines that allow controlled and timed release of the compds. Also described are the prodn. method, the pharmaceutical compns. and the use for prepg. a drug. Thus, nanocapsules were prepd. by using poly(ε-caprolactone) an...

Starting from beta-benzoylpropionic acid we synthesized 3-(aminomethyl)tetralones in which the amino substituent was 4-(N-piperazinyl)-p-fluorobutyrophenone, 4-benzoylpiperidine, 4-hydroxy-4-phenylpiperidine or 4-(o-methoxyphenyl)piperazine. The possible dopamine antagonist activity of these compounds was investigated in both "in vitro" and "in viv...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A series of cyproheptadine related compounds was synthesized and tested pharmacologically. In comparison with cyproheptadine, these compounds do not have a central ring and some contain groups other than N-methyl. Synthesis was carried out with low-valent titanium to generate the exocyclic double bond. The serotoninergic activity of the compounds w...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

For Abstract see ChemInform Abstract in Full Text.

Glucosyl dopamine (DA) derivatives may represent a new class of DA prodrugs that would interact with glucose transporter GLUT-1, present in the blood-brain barrier, and generate DA in the brain. Therefore, compounds bearing the sugar moiety linked to either the amino group or the catechol ring of DA through amide, ester, carbamate, peptide or glyco...

A series of novel long-chain arylpiperazines bearing a coumarin fragment was synthesized and the compounds were evaluated for their affinity at alpha(1), D(2 )and 5-HT(2A) receptors. Most of the new compounds showed high affinity for the three types of receptors alpha(1A), D(2) and 5-HT(2A) which depends, fundamentally, on the substitution of the N...

A series of novel conformationally restricted butyrophenones (6-aminomethyl-4,5,6,7-tetrahydrobenzo[b]furan-4-ones bearing 4-(6-fluorobenzisoxazolyl)piperidine, 4-(p-fluorobenzoyl)piperidine, 4-(o-methoxyphenyl)piperazine, 4-(2-pyridyl)piperazine, 4-(2-pyrimidinyl)piperazine, or linear butyro(or valero)phenone fragments) were prepared and evaluated...

A new approach to deliver dopamine into the central nervous system, based on the use of D-glucose as transportable agent, has been studied. Glycosyl dopamine derivatives bearing the sugar moiety linked to either the amino group or the catechol ring of dopamine through amide, ester or glycosidic bonds were synthesised as potential antiparkinsonian a...

The N-methyl, N-ethyl, and N-n-propyl derivatives of 5-hydoxy- and 10-hydroxy-2,3,12,12a-tetrahydro-1H-[1]benzoxepino[2,3, 4-ij]isoquinolines were prepared as monophenolic ligands for the dopamine receptor and evaluated for their affinity at D(1)-like and D(2)-like subtypes. All compounds showed very low D(1) affinities. This could be ascribed to t...

We describe practical and efficient routes for synthesis of 2-aminomethyl-1,2,3,9-tetrahydro-4H-carbazol-4-ones using the Fischer indole synthesis or palladium-catalysed cyclization methodologies, as well as their affinities for D(2), 5-HT(2A) and 5-HT(2C) receptors, and their activity at the 5-HT(2B) receptor. The most active compounds, 4b (QF 200...

We describe practical and efficient routes for synthesis of 2-aminomethyl-1,2,3,9-tetrahydro-4H-carbazol-4-ones using the Fischer indole synthesis or palladium-catalysed cyclization methodologies, as well as their affinities for D2, 5-HT2A and 5-HT2C receptors, and their activity at the 5-HT2B receptor. The most active compounds, 4b (QF 2003B) and...

A series of novel conformationally restricted butyrophenones (2-(aminoethyl)- and 3-(aminomethyl)thieno- or benzocycloalkanones bearing (6-fluorobenzisoxazolyl)piperidine, (p-fluorobenzoyl)piperidine, (o-methoxyphenyl)piperazine, or linear butyrophenone fragments) were prepared and evaluated as atypical antipsychotic agents by in vitro assays of af...

The effects of two new synthetic compounds showing in vitro catechol-O-methyl transferase (COMT) inhibitor properties were studied in vivo and compared with the effects of nitecapone and Ro-41-0960. QO IA (3-(3-hydroxy-4-methoxy-5-nitrobenzylidene)-2,4-pentanedione), QO IIR ([2-(3,4-dihydroxy-2-nitrophenyl)vinyl]phenyl ketone), nitecapone and Ro-41...

We describe a practical and efficient route for synthesis of 2-aminomethyl-1,2,3,9-tetrahydro-4H-carbazol-4-ones using an effective Fisher indole methodology. The most active compounds, 4b (QF 2003B) and 4c (QF 2004B), with pKi (5-HT2A/D2) ratio of 1.28 show an antipsychotic profile according to Meltzer's classification.

A simple and efficient synthesis of novel 6-aminomethyl-tetrahydroindol-4-ones, which are butyrophenone analogues of molindone, is described. These compounds exhibit potent affinities for D2 and 5-HT2A receptors in vitro. The most active compounds, 6d (QF 0408B) and 6e (QF 0409B), with pKi (5-HT2A/D2) ratios of 1.32 and 1.17 respectively, show an a...

A trial to designde novoa dopamine (DA) receptor ligand was made, taking as the base four structural and electrostatic requirements: (1) a group simulating the interaction of the DA amino group with the TM3 aspartic acid of the receptor, (2) a group that can simulate the interaction of the DAm-hydroxyl group with the TM5 serine of the receptor, (3)...

Starting from benzo- or thienocycloalkaneacetic acids, we have prepared a series of 1-(3-p-fluorobenzoylpropyl)-4-(1-oxo-benzo- or thienocycloalkyl-2-ethyl)piperazines 8a-e containing both semirigid and linear butyrophenones pharmacophores. The affinities of these compounds for dopamine (D2) and 5-hydroxytryptamine (5-HT2A) receptors were evaluated...

Starting from 2-methyl-3-ethyl-1H-4,5,6,7-tetrahydroindol-4-one 3 we have prepared 2-methyl-3-ethyl-5-morpholinoethyl-1H-4, 5,6,7-tetrahydroindol-4-one, (1) and 2-methyl-3-ethyl-5-(4-o-methoxyphenyl-1-piperazinoethyl)-1H-4,5,6,7-tetrahydroindol-4-one (2) as butyrophenone analogues of the neuroleptic molindone. The affinities of these compounds for...

We have synthesized several 3-amino-6-phenyl pyridazines in which the amino substituent is a linear butyrophenone moiety (compounds 8 and 10), a cyclic butyrophenone moiety (compound 3), or a phenylpiperazine fragment (compound 2). Compound 8 potently inhibited [3H]spiperone binding to striatal D2 receptors and [3H]SCH 23390 binding to striatal D1...

Four new 2-(2-piperidinoethyl)benzocycloalkanone derivatives, 20-23, were prepared and evaluated as potential antipsychotic agents in receptor binding assays for dopamine (DA) and 5-HT2A receptors and in functional and behavioral screens. Their affinities for D2 receptors (Ki's in the nanomolar range: 46.7-70.7) and D1 receptors (Ki's in the microm...

A series of cyproheptadine related compounds was synthesized and tested pharmacologically. In comparison with cyproheptadine, these compounds do not have a central ring and some contain groups other than N-methyl. Synthesis was carried out with low-valent titanium to generate the exocyclic double bond. The serotoninergic activity of the compounds w...

The antiserotoninergic activity at the serotonin receptor subtype 2 (5-HT2) of seven new 2-aminoethylbenzocyclanones was determined with respect to serotonin-induced contractions in rat aorta and compared with that of ketanserine (pA2 = 8.87). Competitive antagonism was observed in six compounds (6.72 < or = pA2 < or = 8.12). Three-dimensional stru...

3-Hydrazinocycloheptyl[1,2-c]pyridazine (4) and its hydra-zone derivatives 3-[N1-(isopropylidene)]hydrazinocyclohexyl[1,2-c]pyridazine (5) and 3-[N1-(isobutylidene)]hydrazinocycloheptyl[1,2-c]pyridazine (6) were prepared, and their activity against genetic, neurogenically-induced, and deoxycorticosterone acetate -NaCl-induced hypertension was found...

1. In conscious normotensive rats, hydralazine (5-10 mg kg-1 p.o.) produced a dose-related fall in systolic blood pressure, accompanied by a pronounced increase in heart rate. 2. The tachycardia induced by hydralazine (10 mg kg-1 p.o.) in conscious normotensive rats was strongly inhibited after anaesthesia with urethane (1.26 g kg-1 i.p.). 3. In an...

The affinity of four 3-aminomethyltetralones for 5-HT2 receptors is reported, together with their inhibitory activity against serotonin-induced contractions in rat aorta rings stripped of endothelium. Compound 4, which has a p-fluorobenzoyl-piperidine fragment, exhibited activity similar to that of methysergyde.

Starting from beta-benzoylpropionic acid was synthesized 3-(aminomethyl)tetralones in which the amino substituent was 4-(N-piperazinyl)-p-fluorobutyrophenone (14), 4-benzoylpiperidine (15), 4-hydroxy-4-phenylpiperidine (16) or 4-(o-methoxyphenyl)piperazine (17). The possible dopamine antagonist activity of these compounds was investigated in both '...

The preparation of a series of 3-hydrazinocycloalkyl[1,2-c]pyridazines 7 and some derivatives as hydrazones 8, 9, triazoles 10 and pyrroles 11 are described together with their hypotensive activity in normotensive rats.

The preparation of a series of 3-hydrazinocycloalkyl[1,2-c]-pyridazines 7 and some derivatives as hydrazones 8, 9, triazoles 10 and pyrroles 11 are described together with their hypotensive activity in normotensive rats. Pyridazin-Derivate, 7. Mitt.: Synthese und blutdrucksenkende Wirkung von 3-Hydrazinocycloalkyl[1,2-c]pyridazinen und ihrer Deriva...

The preparation of new 3-hydrazinothieno(2,3-h)cinnolines is described togehter with their hypotensive effects in normotensive rats.Pyridazinderivate, 6. Mitt: Synthese und antihypertensive Eigenschaften von 3-Hydrazinthieno(2,3-h)cinnolinen und ihrer DerivateEs werden die Darstellungen neuer 3-Hydrazinothieneo-(2,3-h)cinnoline and ihrer Derivate s...

The preparation of new 3-hydrazinothieno(2,3-h)cinnolines is described togehter with their hypotensive effects in normotensive rats. Pyridazinderivate, 6. Mitt: Synthese und antihypertensive Eigenschaften von 3-Hydrazinthieno(2,3-h)cinnolinen und ihrer Derivate Es werden die Darstellungen neuer 3-Hydrazinothieneo-(2,3-h)cinnoline and ihrer Derivate...