RESUMEN
Silk fibroin (SF) is a natural protein extracted fromBombyx morisilkworm thread. From its common use in the textile industry, it emerged as a biomaterial with promising biochemical and mechanical properties for applications in the field of tissue engineering and regenerative medicine. In this study, we evaluate for the first time the effects of SF on cardiac bioink formulations containing cardiac spheroids (CSs). First, we evaluate if the SF addition plays a role in the structural and elastic properties of hydrogels containing alginate (Alg) and gelatin (Gel). Then, we test the printability and durability of bioprinted SF-containing hydrogels. Finally, we evaluate whether the addition of SF controls cell viability and function of CSs in Alg-Gel hydrogels. Our findings show that the addition of 1% (w/v) SF to Alg-Gel hydrogels makes them more elastic without affecting cell viability. However, fractional shortening (FS%) of CSs in SF-Alg-Gel hydrogels increases without affecting their contraction frequency, suggesting an improvement in contractile function in the 3D cultures. Altogether, our findings support a promising pathway to bioengineer bioinks containing SF for cardiac applications, with the ability to control mechanical and cellular features in cardiac bioinks.
Asunto(s)
Alginatos , Elasticidad , Fibroínas , Gelatina , Hidrogeles , Miocitos Cardíacos , Alginatos/química , Alginatos/farmacología , Fibroínas/química , Fibroínas/farmacología , Gelatina/química , Hidrogeles/química , Hidrogeles/farmacología , Animales , Miocitos Cardíacos/citología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Bioimpresión , Supervivencia Celular/efectos de los fármacos , Ingeniería de Tejidos , Tinta , Esferoides Celulares/citología , Esferoides Celulares/efectos de los fármacos , Ratas , Contracción Miocárdica/efectos de los fármacosRESUMEN
The synthesis of some 3-(1,3,4-thiadiazol-2-yl)pyrazolo[1,5-a]-pyrimidine derivatives is performed by reacting 2-(3-amino-1,2-dihydro-5-oxo-5H-pyrazol-4-il)-1,3,4- thiadiazoles with 2,4-pentanedione, ethyl 3-oxobutyrate and diethyl ethoxymethylenemalonate. The antimicrobial activity of the synthesized compounds is reported.
Asunto(s)
Antibacterianos/síntesis química , Pirazoles/síntesis química , Pirimidinas/síntesis química , Tiadiazoles/síntesis química , Difusión , Escherichia coli/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Pseudomonas aeruginosa/efectos de los fármacos , Pirazoles/química , Pirazoles/farmacología , Pirimidinas/química , Pirimidinas/farmacología , Staphylococcus epidermidis/efectos de los fármacos , Tiadiazoles/química , Tiadiazoles/farmacologíaRESUMEN
The synthesis of some 2-[1,2-dihydropyrazol-4-yl]-1,3,4-thiadiazole derivatives is performed by reacting 4-dithiocarboxylic acid hydrazides of 3-amino-1,2-dihydro-5H-pyrazol-5-one and 3-amino-1,2-dihydro-1-methyl-5H-pyrazol-5-one with carboxylic acid derivatives. The unusual behaviour of 3-amino-1,2-dihydro-1-methyl-5H-pyrazol-5-one towards acetylating agents is described. The antimicrobial activity of some 2-[1,2-dihydropyrazol-4-yl]-1,3,4-thiadiazole derivatives is tested in a preliminary screening.
Asunto(s)
Antibacterianos/síntesis química , Pirazoles/síntesis química , Tiadiazoles/síntesis química , Bacterias/efectos de los fármacos , Fenómenos Químicos , Química , Pruebas de Sensibilidad Microbiana , Pirazoles/farmacología , Tiadiazoles/farmacologíaRESUMEN
4,7-Dihydro-4-ethyl-2-phenylpyrazolo-[1,5-a]pyrimidin-7-one (FPP028) is the prototype of a class of pyrazolo[1,5-a]pirimidine derivatives that has been shown to possess marked antiinflammatory and analgesic properties; 1,4-dihydro-1-ethyl-7-phenylpyrrolo[1,2-a]pyrimidin-4-one (FPP129) is a new compound belonging to a series of pyrrolo[1,2-a]pirimidine derivatives that has been synthetized in an attempt to reduce certain toxic effects observed with FPP028. To evaluate these two compounds more fully, in the present study we determined the LD50 of FPP129 in mice and assessed its activity in different experimental inflammation models. Ulcerogenic properties of FPP129 were evaluated by the test of stress-induced ulcer in rats. We also studied the in vitro and ex vivo effects of both FPP028 and FPP129 in a series of platelet-aggregation experiments using either arachidonate or collagen as aggregating agents. In the carraggeenan-induced paw edema, FPP129 exerted a marked anti-inflammatory activity with an ED50 of 22.2 mg/kg. FPP129 inhibited also the edema induced by concanavalin-A or Paf-acether. The in vitro anti-aggregatory activity of FPP028 was shown to be much less than that of indomethacin, thus confirming the hypothesis that the compound is a very weak inhibitor of cyclooxygenase. Ex vivo, both FPP028 and FPP129 were shown to exert no antiaggregatory effect in rabbits after administration of doses equal to the ED50. No ulcerogenic activity was found with FPP129, this result being consistent with previous observations on FPP028. Our data show tha FPP028 and FPP129 do not share a typical mechanism of action (cyclooxygenase inhibition) found with the majority of nonsteroidal antiinflammatory drugs. Nonetheless, the antiinflammatory properties of these compounds, together with their lack of ulcerogenic activity, indicate that both FPP028 and FPP129 are potentially interesting for future therapeutic use.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Pirazoles/farmacología , Pirimidinas/farmacología , Pirroles/farmacología , Animales , Carragenina , Edema/inducido químicamente , Edema/tratamiento farmacológico , Humanos , Técnicas In Vitro , Indometacina/farmacología , Dosificación Letal Mediana , Masculino , Inhibidores de Agregación Plaquetaria , Pirazoles/toxicidad , Pirimidinas/toxicidad , Pirroles/toxicidad , Ratas , Restricción Física , Úlcera Gástrica/inducido químicamenteRESUMEN
2-Amino-4-phenylpyrrolyl-3-carbonitrile (I) was reacted with ethyl formylacetate sodium salt affording 1,4-dihydro-4-oxo-7-phenylpyrolo[1,2-a]pyrimidin-8-carbonitrile (II), which was alkylated with EtI to give (III), which in turn was hydrolyzed to (IV). Treatment of both (III) and (IV) with 99% H3PO4 at approximately 200 degrees gave 1,4-dihydro-1-ethyl-7-phenylpyrrolo-[1,2-a]pyrimidin-4-one (V) whose structure was ascertained by an unequivocal synthesis starting from (I) and diethyl ethoxymethylenmalonate. Compound (V) was prepared in order to test its pharmacological properties in comparison with 4,7-dihydro-4-ethyl-2-phenylpyrazolo[1,5-a]pyrimidin-7-one, which showed an antiinflammatory activity comparable to that of phenylbutazone and indomethacine, and which was found devoid of ulcerogenic properties.
Asunto(s)
Antiinflamatorios/síntesis química , Pirimidinas/síntesis química , Pirroles/síntesis química , Animales , Fenómenos Químicos , Química , Pirimidinas/efectos adversos , Pirimidinas/farmacología , Pirimidinas/toxicidad , Pirroles/efectos adversos , Pirroles/farmacología , Pirroles/toxicidad , Úlcera Gástrica/inducido químicamenteRESUMEN
The synthesis of some 2-[5-amino-1-methyl-3-oxo-4-pyrazolynyl]-1,3,4-thiadiazole derivatives is accomplished by reacting 5-amino-1-methyl-3-oxopryrazolynyl-4-dithiocarbohydrazide with carboxylic acid derivatives. The structure of the compounds obtained is verified by means of 1H and 13C-N.M.R. spectra. Antimicrobial and antifungal activity of some of the described compounds was tested in a preliminary screening.
Asunto(s)
Antiinfecciosos/síntesis química , Pirazoles/síntesis química , Tiadiazoles/síntesis química , Antifúngicos/síntesis química , Fenómenos Químicos , Química , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Pirazoles/farmacología , Tiadiazoles/farmacologíaRESUMEN
The activity of 2-phenylpyrazolo-4-ethyl-4,7-dihydro [1,5a]pyrimidin-7-one (FPP028), a non-acidic, analgesic, antipyretic, and anti-inflammatory compound, was investigated in a number of pharmacological tests performed in rats. The anti-inflammatory properties of FPP028 were evaluated through the carrageenan induced paw edema and the cotton pellet induced granuloma and compared with the activity of indomethacin, phenylbutazone, and isoxicam; as a result, the activity of FPP028 was shown to be similar to that of the latter compounds. To assess the analgesic properties of FPP028 in comparison with indomethacin and phenylbutazone, the Randall and Sellitto and the mouse-writhing tests were used; in both tests, FPP028 demonstrated a significant analgesic activity. FPP028 was shown to possess antipyretic properties in the test of yeast-induced pyrexia. The gastro-erosive activity of phenylbutazone and FPP028 was studied in restraint-stressed rats; in such test the ulcerogenic activity of phenylbutazone appeared to be dose-related; conversely, FPP028 demonstrated a gastro-protective effect since the number of gastric lesions induced either by stress or phenylbutazone treatment was decreased bu FPP028. Our data show that FPP028 is endowed with most of the pharmacological properties of the classic antiinflammatory drugs. Further studies are however needed to more fully elucidate its mechanism of action because our in-vivo data indicate that FPP028 is not an inhibitor of prostaglandin biosynthesis.
Asunto(s)
Antiinflamatorios/farmacología , Piroxicam/análogos & derivados , Pirazoles/farmacología , Pirimidinas/farmacología , Adrenalectomía , Animales , Antiinflamatorios/toxicidad , Antiinflamatorios no Esteroideos , Aspirina/farmacología , Edema/tratamiento farmacológico , Ácido Gástrico/metabolismo , Granuloma/tratamiento farmacológico , Cobayas , Técnicas In Vitro , Indometacina/farmacología , Masculino , Ratones , Fenilbutazona/farmacología , Prostaglandinas/biosíntesis , Pirazoles/toxicidad , Pirimidinas/toxicidad , Ratas , Ratas Endogámicas , Úlcera Gástrica/inducido químicamente , Tiazinas/farmacologíaRESUMEN
Syntheses of some pyrazolo[1,5-a]pyrimidines were performed in order to study the relationship between structural modifications on the parent 4,7-dihydro-2-phenylpyrazolo[1,5-a]pyrimidin-7-one (1) and their antiinflammatory properties. The modifications carried out were introduction and functionalization of a longer side chain at the 4-position, substitution of the hydrogen atom at the 3-position, and replacement of the phenyl group with a 4-methylphenyl, methyl, or hydrogen substituent. 4-Ethyl-4,7-dihydro-2-phenylpyrazolo [1,5-a]pyrimidin-7-one (3) showed the highest activity and a better therapeutic index than phenylbutazone and indomethacin, used as reference drugs. All other changes at the 3-, 5-, and 6-positions, as well as the replacement of the phenyl group at position 2, caused a marked decrease of activity. Compound 3 was found devoid of ulcerogenic activity and was probably endowed with antiulcerogenic properties.
Asunto(s)
Antiinflamatorios no Esteroideos , Pirazoles/síntesis química , Pirimidinas/síntesis química , Úlcera/inducido químicamente , Animales , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/toxicidad , Indometacina/farmacología , Masculino , Fenilbutazona/farmacología , Pirazoles/toxicidad , Pirimidinas/toxicidad , RatasRESUMEN
The paper reports the inhibitory activity (ID50) of a series of 2-phenylpyrazolo [1,5-a]pyrimidines on prostaglandin synthetase of guinea-pig lung homogenate in comparison with indomethacin. In vivo studies showed that some of these compounds possess interesting antiinflammatory, antipyretic and analgesic properties, as compared to those of classic non steroid antiinflammatory drugs like aspirin or phenylbutazone.
Asunto(s)
Antiinflamatorios/síntesis química , Pirazoles/síntesis química , Pirimidinas/síntesis química , Animales , Antiinflamatorios no Esteroideos , Aspirina/farmacología , Carragenina/antagonistas & inhibidores , Inhibidores de la Ciclooxigenasa , Pirazoles/farmacología , Pirimidinas/farmacología , Ratas , Factores de TiempoRESUMEN
2-Phenylpryrazolo [1,5-a]pyrimidine (I) 4,7-dihydro-2-phenylpyrazolo [1,5-a]pyrimidin-7-one (II) and 4,5-dihydro-2-phenylpyrazolo [1,5-a]pyrimidin-5-one (III) are prepared. Because of the interesting antipyretic, hypothermizing and anti-inflammatory properties of some of their derivatives, the above mentioned compounds are used as reference compounds in a Q.S.A.R. study still in progress. Methylation of (II) and (III) with (CH3)2SO4 and CH2N2 gives methylderivatives whose structure is determined by spectroscopic means.
Asunto(s)
Antiinflamatorios no Esteroideos/síntesis química , Pirazoles/síntesis química , Pirimidinonas/síntesis química , Animales , Fenómenos Químicos , Química , Pirazoles/farmacología , Pirimidinonas/farmacologíaRESUMEN
The synthesis of ethyl 2-phenyl-7-alkyl (or 7-phenyl)pyrazolo[1,5-a]pyrimidine-5-carboxylate and ethyl 2-phenyl-7-alkyl (or 7-phenyl)pyrazolo[1.5-a]pyrimidine-6-carboxylate are reported. Decarboxylation of the acids, obtained by hydrolysis of the above esters, yields the same compounds. N.M.R. data on the reduction products of the ethyl 6-carboxylate confirm all the assigned structures.
Asunto(s)
Pirazoles/síntesis química , Acetatos , Ácidos Carboxílicos/síntesis química , Hidrólisis , Espectroscopía de Resonancia Magnética , Pirimidinas/síntesis química , PiruvatosRESUMEN
The paper reports the pharmacological activity in vitro and in vivo of a series of pyrazolo[1,5-a]pyrimidine derivatives. Some of these compounds have proved to be active in decreasing the body temperature. They are also very active inhibitors of the guinea-pig lung prostaglandin-sintetase.
Asunto(s)
Pirazoles/farmacología , Pirimidinas/farmacología , Animales , Temperatura Corporal/efectos de los fármacos , Inhibidores de la Ciclooxigenasa , Cobayas , Técnicas In Vitro , Masculino , Inhibidores de la Monoaminooxidasa , RatasRESUMEN
Structures of condensation products between 3-phenyl-5-aminopyrazole and ethyl ethoxymethylenacetoacetate and ethyl acetonoxalate are demonstrated, namely ethyl 2-phenyl-7-methylpyrazolo[1,5-a]pyrimidin-6-carboxylate and ethyl 2-phenyl-7-methylpyrazolo[1,5-a]pyrimidin-5-carboxylate. Studies on antipyretic and hypothermizing activity of the acid derived from the latter and of other compounds are reported.
Asunto(s)
Antiinflamatorios no Esteroideos/síntesis química , Pirazoles/síntesis química , Pirimidinas/síntesis química , Animales , Antiinflamatorios no Esteroideos/uso terapéutico , Fiebre/tratamiento farmacológico , Masculino , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , RatasRESUMEN
The synthesis of 1,2,4,6-tetrahydro-2-methyl-3-hydroxypyrazolo [3,4-d] [1,3]thiazine-4,6-dithione is described. By spectroscopic methods the anphionic structure of this and other related compounds is demonstrated. In addition, the action of alkylating reagents upon pyrazolo-[3,4-d] [1,3]thiazine-4,6-dithionic compounds is examined and described. The biological activity of the new synthesized compounds is reported.
Asunto(s)
Pirazoles/síntesis química , Tiazinas/síntesis química , Animales , Gluconeogénesis/efectos de los fármacos , Técnicas In Vitro , Espectroscopía de Resonancia Magnética , Métodos , Anafilaxis Cutánea Pasiva/efectos de los fármacos , Pirazoles/farmacología , Ratas , Espectrofotometría , Tiazinas/farmacologíaRESUMEN
In the course of researches on pyrazolo[1,5-a]pyrimidine compounds, methylation reactions with (CH3)2SO4 and CH2N2 are studied. Methylderivatives structure is assigned by means of a spectroscopic investigation. A relationship between the kind of reagent and the methyl group position is stressed.
Asunto(s)
Pirimidinas/análisis , Fenómenos Químicos , Química , Ciclización , Indicadores y Reactivos , Espectroscopía de Resonancia Magnética/métodos , Metilación , Espectrofotometría Infrarroja/métodos , Espectrofotometría Ultravioleta/métodosRESUMEN
Compounds of the 7H-furo-[3,2-g]-1-benzopyran system are prepared by condensation of kellinone with malonic acid derivatives. The 4,9-dimethoxy-5-methyl-7-H-furo-[3,2g]-1-benzopyran-7-one-6-carboxylic acid chloride reacts with aliphatic and heterocyclic amines and with aliphatic aminoalcohols giving amides that could have pharmacological interest.
Asunto(s)
Benzopiranos/síntesis química , Amidas/síntesis química , Aminas , Furanos/síntesis químicaRESUMEN
The reaction between 1,2-diphenyl-4-bis-(methylthio)methylenepyrazolidin-3,5-dione with serine and cysteine and their derivatives is described. The structure of the resulting compounds is assigned spectrophotometrically.