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M Mazzei

Publications and source records attributed to M Mazzei.

At least 55 records · Page 3Linked to original sources
PubMed1988

Effects of insulin and dexamethasone on adenine nucleotide levels in cultured hepatocytes from adult rat.

Insulin and dexamethasone, usually added to culture media, play an important role in maintaining the survival of functional hepatocytes. Adenine nucleotide concentrations and energy charge values of cultured hepatocytes were determined to investigate the relationship between the beneficial effects of these hormones and the energy status of the cells. The results indicate that insulin and dexamethasone are essential in maintaining the metabolic competence of cultured hepatocytes and that this correlates with the absolute concentration of ATP rather than with the energy charge.

Adenine Nucleotides↗
PubMed1988

Formation of 2,6-dimethoxy-1,4-benzoquinone, a highly genotoxic compound, from the reaction of sodium nitrite with the sympathomimetic drug dimethophrine in acidic aqueous solution.

Because of the genotoxic effects shown by Dimethophrine (DMP) nitrosation mixtures, the interaction between DMP hydrochloride and sodium nitrite in acidic aqueous solution at 37 degrees was investigated in a wide range of reagent concentrations and molar ratios, reaction times and pH values. Actually, depending on the operating conditions, it was possible to detect variable amounts of 2,6-dimethoxy-1,4-benzoquinone (DMBQ), a highly genotoxic compound, but no N-nitrosoderivative. The highest conversion of DMP into DMBQ was obtained when concentrated acidic solutions of DMP and NaNO2 (molar ratio 1:1.9) reacted at pH 3.0-4.0 (50-60% after 1 hour, depending on the pH conditions). When DMP hydrochloride and NaNO2 (molar ratio 1:0.95) were allowed to react at pH 3.5 in a more diluted solution, to mimic gastric conditions, the conversion of DMP into DMBQ after 20 min was about 3%. The breakdown of DMP can be prevented by adding suitable amounts of ascorbic acid to the reagents.

Benzoquinones↗
PubMed1988

[Derivatives of pyrimidine 1,2-condensate. IV. Synthesis and pharmacological properties of the N,N-disubstituted 4-amino-2H-pyrido(1,2-a)pyrimidin- 2-ones and 2-amino-4H-pyrido(1,2-a)pyrmidin-4-ones].

The N,N-disubstituted 4-amino-2H-pyrido[1,2-a]pyrimidin-2-ones (III) and isomer 2-amino-4H-pyrido[1,2-a]pyrimidin-4-ones (IV) were obtained from the reaction of 2-aminopyridine with the N,N-disubstituted ethyl malonamate/phosphorus oxychloride reagent (II), in refluxing 1,2-dichloroethane. 2-[(N-Benzyl, N-ethyl)amino]derivative (IV b) was also prepared in excellent yield by treating 2-chloro-4H-pyrido[1,2-a]pyrimidin-4-one (V) with N-ethylbenzylamine. Finally, hydrogenation (Raney Nickel) of 4-[(N-ethyl,N-phenyl)amino]-2H-pyrido[1,2-a]pyrimidin-2-one (III e) afforded 6,7,8,9-tetrahydroderivative (VI) which in turn was treated with potassium borohydride to give 1,6,7,8,9,9a-hexahydroderivative (VII). Several compounds described in the present paper, along with some other compounds (III) and (IV) previously synthesized by us (1,2), were tested for various pharmacological activities. The antiallergic activity (PCA in the rat), even though found in several compounds examined, turned out to be submaximal in any case, in spite of the high dose administered (500 mg/kg p.o. as a rule). The most active compound (the activity being estimated at 0.42 times that of thiaramide hydrochloride) was the 4-aminoderivative (III e). The 2-aminoderivatives (IV) series, was found to have marked antiinflammatory properties (carrageenin oedema in the rat); nevertheless, this activity was related to toxic symptoms with the exception of compound (IV b), almost asymptomatic at the administered dose (200 mg/kg p.o.). Moreover the 2-aminoderivatives (IV) generally showed weak adrenolitic activity in vitro (rat seminal vesicles), which was estimated to be from 100 to 1000 times less than that of phenoxybenzamine.

Aminopyridines↗
PubMed1988

Cytotoxic, DNA-damaging and mutagenic properties of 2,6-dimethoxy-1,4-benzoquinone, formed by dimethophrine-nitrite interaction.

In conditions similar to those occurring in the stomach, the sympathomimetic drug dimethophrine was found to react with nitrite yielding 2,6-dimethoxy-1,4-benzoquinone (DMBQ). The in vitro and in vivo studies carried out to evaluate the capability of DMBQ to produce cytotoxic and genotoxic effects provided the following results. A dose-related reduction of V79 cells plating efficiency was observed for DMBQ concentrations ranging from 10 to 80 microM; a similar reduction in the fraction of viable cells excluding trypan blue occurred after exposure to 4-fold higher concentrations. A dose-dependent amount of DNA fragmentation was revealed by the alkaline elution technique either in V79 cells exposed to DMBQ concentrations ranging from 10 to 80 microM or in kidney, gastric mucosa and brain of rats treated with single p.o. doses ranging from 33 to 300 mg/kg. Both in vitro and in vivo DNA lesions were largely repaired within 24 hr, but their promutagenic character was demonstrated by the induction of 6-thioguanine-resistance in V79 cells. Primary cultures of rat hepatocytes displayed a greater resistance to the cytotoxic and DNA-damaging activities of DMBQ, and did not exhibit a clear evidence of DNA repair synthesis. Similarly, DNA fragmentation was practically undetectable in the rat liver. Therefore, DMBQ should be considered as a direct-acting genotoxic chemical which is metabolized to less, or nonreactive, species. These findings suggest that DMBQ could produce genotoxic effects in patients taking dimethophrine.

Animals↗
PubMed1987

Alkaline extraction and reverse-phase high-performance liquid chromatography of adenine and pyridine nucleotides in human platelets.

The levels of adenine (ATP, ADP, AMP) and pyridine (NAD, NADH) nucleotides in human platelets have been measured by a simple and reproducible method. A rapid alkaline extraction allows a complete recovery of the compounds concerned. The metabolic ATP and ADP in the cytosolic fraction, the amount released upon thrombin stimulation, and the ADP bound to F-actin have also been evaluated. Analysis was performed by reverse-phase, isocratic high-performance liquid chromatography on a 5-microns Lichrosorb RP-18 column with uv detection at 254 nm.

Adenine Nucleotides↗
PubMed1986

[Derivatives of 1,2-condensed pyrimidines. II. Synthesis and pharmacological study of N,N-disubstituted 5-amino-7H-thiazol [3,2-a]pyrimdine-7-ones].

Reaction of 2-aminothiazole with the N,N-dialkyl or (N-alkyl, N-phenyl) ethoxycarbonylacetamide/POCl3 reactant (I), in refluxing 1,2-dichloroethane, yielded the corresponding N,N-disubstituted 5-amino-7H-thiazolo[3,2-a]pyrimidin-7-ones (VII) along with lower quantities of isomeric N,N-disubstituted 7-amino-5H-thiazolo[3,2-a]pyrimidin-5-ones (VIII). Structures attributed to isomeric compounds (VII) and (VIII) were supported both by spectroscopic and chemical evidences. Some compounds (VII) were submitted to pharmacological investigation and results are described: only (N-alkyl, N-phenyl)derivatives (VII f,g) showed a significant, even if mild, activity as peripheral analgesics.

Animals↗
PubMed1986

[3-Dialkylamino-substituted 2H-1,4-benzoxazines].

N,N,N',N'-Tetrasubstituted 2-(2-aminophenoxy)malonamides (IX) in the presence of phosphorus oxychloride led to the formation of N,N-dialkyl-3-(dialkylamino)-2H-1,4-benzoxazine-2-carboxamides (XII). In the same way 2-(2-amino-3-pyridyloxy)-N,N,N',N'-tetraethylmalonamide (X) yielded 3-(diethylamino)-N,N-diethyl-2H-pyrido[3,2-b] [1,4]oxazine-2-carboxamide (XIII). Also N,N-dialkyl-2-(2-aminophenoxy)acetamides (XIV) by the action of phosphorus oxychloride afforded 3-(dialkylamino)-2H-1,4-benzoxazines (XV). Some compounds when submitted to pharmacological screening showed a weak depressant activity in the Irwin test.

Analgesics↗
PubMed1986

[Chemistry and pharmacology of pyran derivatives. XVII. Synthesis of 2-(dialkylamino)-5-hydroxychromones and their transformation to derivatives of 2H-pyran[4,3,2-de]-1-benzopyran].

Through the reaction of resorcin with N,N-dialkylethoxy-carbonylacetamides in suitable conditions 2-(dialkylamino)-5-hydroxychromones (II) were available. Transformation of these compounds into [5-acetoxy-2-(dialkylamino)-4H-chromen-4-ylidene] malononitriles (VII) by reaction with malononitrile in acetic anhydride and treatment of (VII) with hydrochloric acid gave rise to the formation of 5-(dialkylamino)-2-imino-2H-pyrano [4,3,2-de]-1-benzo-pyrans (VIII). Furthermore 5-hydroxychromones (II) when treated with methyl iodide gave the corresponding 5-methoxychromones (III) which in turn yielded 4H-chromen-4-ylidene derivatives (X) by reaction with malononitrile in acetic anhydride. The hydrolysis of the latter compounds with hydrochloric acid resulted in the formation of 2-(dialkylamino)-4-methyl-5-methoxychromenilium salts (XI). Among the compounds which were submitted to pharmacological screening for their antiallergic properties 5-methoxychromone (III a) and 2H-pyrano [4,3,2-de]-1-benzopyran (VIII b) showed a notable activity but also high toxicity.

Animals↗
PubMed1985

[Chemistry and pharmacology of pyran derivatives. 16. Derivatives of 2-(dialkylamino)-7-methoxychromone with antiallergic activity].

Since 2-(diethylamino)-7-methoxychromone (III a) showed remarkable activity in the rat PCA test, some modifications to its structure were made. For instance new substituents such as chlorine or nitro group were introduced into the molecule and the diethylamino group modified. Thus, 2-(ethylamino)-7-methoxychromone (IX) was prepared by treating 3-methoxyphenol with N-ethylethoxycarbonylacetamide in the presence of phosphorus oxychloride. In this case a small amount of 4-chloro-7-methoxycoumarin was also isolated from the reaction mixture. Moreover compounds (XIV), (XV), (XVII) structurally related to sodium cromoglycate were prepared. The pharmacological screening of some compounds showed a useful antiallergic activity.

Animals↗
PubMed1979

[Chemical and pharmacological research on pyran derivatives. XIII. Derivatives of 2H-pyrano/3,2-c/quinoline].

Treatment of N-alkylanilines or diphenylamine with N,N-dialkylethoxycarbonylacetamides in the presence of phosphorus oxychloride afforded 6-alkyl(phenyl)-4-dialkylaminopyrano [3,2-c] quinoline-2,5-(6H)-diones, two molecules of amide being involved in the reaction. In some instances 6-alkyl(phenyl)-4-alkylaminopyrano [3,2-c] quinoline-2,5(6H)-diones were obtained through a partial dealkylation of the amino group. Pharmacological evaluation of some compounds showed no activity on the CNS.

Animals↗
PubMed1979

[Chemical and pharmacological research on pyran derivatives. XII. Bis-(beta-chloroethyl)amino-substituted chromones and benzochromones].

By the reaction of phenols or naphthols with N,N-bis-(beta-methoxyethyl)ethoxycarbonylacetamide in the presence of phosphorus oxychloride the preparation of bis-(beta-methoxyethyl)amino substituted chromones or benzochromones was achieved. Treatment of these compounds with hydriodic acid at 95 degrees and then with thionyl chloride gave rise to the formation of the corresponding bis-(beta-chloroethyl)amino derivatives. When beta-naphthols reacted with N-ethoxycarbonylacetylmorpholine 1-oxo-3-morpholino-1H-naphtho[2,1-b]pyrans were obtained. These compounds as well as the corresponding 3-bis-(beta-methoxyethyl)amino derivatives afforded 1-oxo-3-bis-(beta-iodoethyl)amino-1H-naphtho[2,1-b]pyrans by treatment with hydriodic acid at reflux. The latter compounds were also easily transformed into 3-bis-(beta-chloroethyl)amino derivatives by reaction with phosphorus oxychloride in N,N-dimethylformamide. Pharmacological screening of some of the compounds described indicated no tumor-inhibiting activity.

Animals↗
PubMed1978

[Chemical and pharmaceutical research on pyran derivatives. XI. Synthesis of 2-dialkylamino-4-oxo-10-methyl-4H-naphtho[2,3b]pyrans].

Reaction of N,N-dialkylethoxycarbonylacetamides with 1-methyl-2-naphthol, in the presence of phosphorus oxychloride, gave rise to the formation of 2-dialkylamino-4-oxo-10-methyl-4H-naphtho[2,3-b] pyrans through the preliminary attack of the amide-phosphorus oxychloride reactant at the phenolic hydroxyl and cyclization at position 3 of the naphthalene moiety. However when (N-alkyl,N-phenyl)ethoxycarbonylacetamides were used in the reaction an ortho position of the N-phenyl group was involved in the cyclization and 1-alkyl-2(1'-methyl-2'-naphthoxy)-4-quinolones were achieved. Pharmacological investigation showed that some naphtho[2,3-b]pyran derivatives have neurotropic activity of the sedative, anticonvulsant and antidepressant type very similar to that shown by previously studied 1-oxo-3-dialkylamino-1H-naphtho[2,1-b]pyrans (5).

Amphetamine↗
PubMed1977

[Chemical and pharmacological research on pyran derivatives. VII. Derivatives of naphto/1',2':5,6/pyran/2,3-c/pyrazole and of 12H-naphto/1',2':5,6/pyran/2,3-d/pyrimidine].

Reaction of substituted 1-oxo-3-dialkylamino-1H-naphtho[2,1-b]pyrans with N,N-dimethylformamide in the presence of phosphorus oxychloride afforded the corresponding substituted 1-oxo-2-formyl-3-dialkyl-amino-1H-naphtho[2,1-b]pyrans. Condensation of substituted 1-oxo-2-formyl-3-dimethylamino-1H-naphtho[2,1-b]pyrans with hydrazine or monosubstituted hydrazines led to the formation of 11-oxo-8H,11H-naphtho[1',2':5,6]pyrano[2,3-c]pyrazole derivatives through the intermediate hydrazones and subsequent cyclization. Similarly, condensation with acetamidine or guanidine gave rise to the formation of 12-oxo-12H-naphtho[1',2':5,6]pyrano[2,3-d]pyrimidine derivatives. Some of these compounds were tested for their pharmacological properties, but no noteworthy activity was observed.

Animals↗
PubMed1977

[Chemical and pharmacological research on pyran derivatives. VIII. Synthesis of 2-dialkylamino-7-methoxychromones and derivatives].

2-Dialkylamino-7-methoxychromones were prepared by reaction of a m-methoxyphenol with N,N-dialkylethoxycarbonylacetamides in the presence of phosphorus oxychloride. Treatment of such compounds with 57% hydriodic acid resulted in the formation of the corresponding 7-hydroxy derivatives. These latter, treated with dialkylamines and formaldehyde, were transformed into the 8-dialkylaminomethyl derivatives. On the other hand the reaction of 2-dialkylamino-7-methoxychromones with morpholine and formaldehyde, in the presence of acetic acid, led to the formation of the corresponding 3-morpholinomethyl derivatives. Pharmacological investigation showed that 2-dialkylamino-7-hydroxy-chromones were without effect, whereas all other compounds tested had a clear, but generally weak, CNS stimulant activity.

Animals↗
PubMed1975

[Chemical and pharmacological research on derivatives of 1H-naphto/2,1-b/pyran. IV. Substituted 1-oxo-3-dialkylamino-1H-naphto/2,1-b/pyrans].

Reaction of N,N-dialkylethoxycarbonylacetamides with substituted beta-naphthols in 3 or 6 or 7 positions with halogen, alkyl, methoxycarbonyl, methoxyl, ethoxyl in the presence of phosphorus oxychloride, led to the formation of 1-oxo-3-dialkylamino-1H-naphtho[2,1-b]pyrans bearing substituents in 5 or 8 or 9 positions, respectively. Moreover, on account of the chemical nature of such substituents, suitable chemical transformations of these compounds afforded some other 1H-naphtho[2,1-b]pyran derivatives. Pharmacological tests showed that anticonvulsant activity was improved by introduction of methoxy or ethoxy group in 9 position of several 1-oxo-3-dialkylamino-1H-naphtho[2,1-b]pyrans.

Anticonvulsants↗
PubMed1975

[Chemical and pharmacological research on derivatives of 1H-naphtho/2,1-b/pyran. V. Behavior of some 1-oxo-3-dialkylamino-1H-naphtho/2,1-b/pyrans substituted in the Mannich reaction].

1-Oxo-3-dialkylamino-1H-naphtho [2,1-b] pyrans substituted in positions 5, 8 or 9 with halogen, alkyl, alkoxycarbonyl, hydroxyl, methoxyl, by the Mannich reaction will yield the corresponding 2-dialkylamino-methyl derivatives when a correct amount of acetic acid is present in the reaction mixture. Excess acid will give rise to the formation of substituted 1-oxo-2-[(1'-oxy-3'-oxo-3'H-naphtho [2',1'-b']pyran-2'-yl)methyl]-3-dialkylamino-1H-naphtho [2,1-b] pyrans when the group in the 3 position is dimethylamino or N-pyrrolidyl. In a few cases Mannich bases were accompanied by an appreciable quantity of substituted 2,2'-methylenebis (1-oxo-3-dialkylamino-1H-naphtho-E12,1-B] PYRANS). Therefore, these compounds were synthesized with excellent yields by treating Mannich bases with acetic anhydride. The behavior of some compounds in the acidic hydrolysis was also considered. Some Mannich bases of 1-oxo-3-dialkylamino-9 methoxy-1H-naphtho-[2,1-b] pyrans showed a more specific anticonvulsant activity than the parent compounds.

Animals↗