RESUMO
Mindfulness-based stress reduction, a complementary and alternative therapy, is able to decrease cancer-related fatigue, and stress and to improve the quality of life in cancer patients. Some studies evaluated if mindfulness-based stress reduction could improve some cardiometabolic and cancer risk factors, including systemic chemokines, growth factors, and pro-inflammatory biomarkers (e.g., C-reactive protein, Interleukin-1). In this narrative review, we highlight the pleiotropic beneficial effects of mindfulness-based stress reduction and its clinical impact on cardiovascular and cancer risk factors among patients with cancer in different stages. Moreover, improvements in the overall quality of life, sleep quality, and immune functions [changes in plasma levels of interleukin-4 (IL-4), interferon-γ (INF-γ), and interleukin-10 (IL-10)] will also be discussed. Albeit few clinical studies available in the literature, evidenced the beneficial effects of mindfulness-based stress reduction on the immune and cardiometabolic profile in cancer patients, providing important insights into the closest collaboration between psycho-oncologists, oncologists, and cardiologists.
Assuntos
Doenças Cardiovasculares , Atenção Plena , Neoplasias , Humanos , Qualidade de Vida , Estresse Psicológico/terapia , Estresse Psicológico/etiologia , Fatores de Risco , Neoplasias/terapia , Doenças Cardiovasculares/prevenção & controleRESUMO
A new series of 2-(4- and 3-substituted phenyl)-3-[3-(N,N-dimethylamino) propyl]-1,3-thiazolidin-4-ones were synthesized, characterized, and evaluated for their ability to inhibit the contractions induced by histamine on guinea pig ileum. The measurement of pA2 values suggested that the reported compounds showed H1-antagonism. The more active compounds 5, 9, and 13 exhibited activity close to that of mepyramine.
Assuntos
Antagonistas dos Receptores Histamínicos H1/síntese química , Tiazóis/síntese química , Animais , Feminino , Cobaias , Antagonistas dos Receptores Histamínicos H1/farmacologia , Íleo/efeitos dos fármacos , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Masculino , Relação Estrutura-Atividade , Tiazóis/farmacologia , Difração de Raios XRESUMO
We report evidence of an unusual C-H--O interaction between an alpha-methylene hydrogen of the alkylamine chain of substituted (N,N-dimethylamino)propyl-azetidinones, substituted (N,N-dimethylamino)propyl-thiazolidinones and substituted (N,N-dimethylamino)propyl-thiazinone and the lactam carbonyl oxygen. NMR analysis results, supported by molecular mechanic predictions, were in agreement with ab initio calculations. The observed interaction shorting the nitrogen-nitrogen distance in the H1-histamine antagonist, 2-(4-methylphenyl)-3-[3-(N,N-dimethylamino)propyl]-1,3-thiazolidin-4-one (1) could explain its fitting with the H1-antihistaminic pharmacophoric model and the high antihistaminic activity.
Assuntos
Lactamas/química , Modelos Químicos , Tiazóis/química , Alquilação , Simulação por Computador , Antagonistas dos Receptores Histamínicos H1/química , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética , Nitrogênio/química , Oxigênio/química , Prótons , Termodinâmica , Tiazóis/síntese químicaRESUMO
A series of thiazolidinones related to loperamide was synthesized and evaluated for antidiarrhoeal activity in mice, using the castor oil test. Of five compounds tested, antidiarrhoeal activity was found only for 2-(p-nitrophenyl)-3-¿3-[(4-(p-chlorophenyl)-4-hydroxy)piperidino]ethyl¿- 1,3-thiazolidin-4-one. The compound was less active than loperamide (ED50 values = 48.7 (24.8-95.6) and 0.91 (0.24-3.40) mg kg-1 respectively), but was also less toxic (LD50 values = 745.9 (545.2-929.8) and 108.9 (85.5-138.7) mg kg-1, respectively). Its antidiarrhoeal activity was counteracted by naloxone. Our results support the hypothesis that this compound, like loperamide, is an opiate-receptor agonist.
Assuntos
Antidiarreicos/uso terapêutico , Diarreia/tratamento farmacológico , Loperamida/análogos & derivados , Loperamida/uso terapêutico , Animais , Óleo de Rícino/toxicidade , Diarreia/induzido quimicamente , Dose Letal Mediana , Loperamida/toxicidade , Masculino , Camundongos , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologiaRESUMO
A series of 1-(p-substituted)phenyl-3-(p-alkoxy)phenyl-4-phenyl-azetidin-2-one s 1a-20a, was synthesized and characterized. Their antimicrobial activity, against Gram+ and Gram- bacteria and Fungi, was tested. The compounds 8a, 13a, 14a, 18a and 6a, 9a, 10a showed remarkable activity respectively against Pseudomonas aeruginosa and against Fungi.
Assuntos
Antibacterianos/síntese química , Antifúngicos/síntese química , Azetidinas/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Azetidinas/química , Azetidinas/farmacologia , Testes de Sensibilidade Microbiana , Relação Estrutura-AtividadeRESUMO
4-hydroxy-isophthalaldehyde acid (1), its alkyl esters (methyl, ethyl, propyl and butyl) and alkyl ethers (propyl, butyl, pentyl and esyl), as well as 6-hydroxy-isophthalaldehyde acid (2) ita alkyl esters (methyl and ethyl), 4-hydroxy-5-iodo-isophthalaldehyde acid (3) and its methyl ester were synthesized and characterized. Antimicrobial and antifungal activity was tested and the LD50 of the most active compound 4 was determined.
Assuntos
Anti-Infecciosos/síntese química , Ácidos Ftálicos/síntese química , Animais , Antibacterianos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/toxicidade , Fungos/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Camundongos , Testes de Sensibilidade Microbiana , Ácidos Ftálicos/farmacologia , Ácidos Ftálicos/toxicidade , Espectrofotometria InfravermelhoRESUMO
The N-(2-hydroxy-5-carboxy-benzyliden)-4-substituted anilines (1-6) and the corresponding 5-carbomethoxy derivatives (7-12) were synthesized and characterized. Antimicrobial and antifungal activity was tested against Gram+ and Gram- bacteria and Fungi.
Assuntos
Compostos de Anilina/síntese química , Anti-Infecciosos/síntese química , Compostos de Anilina/farmacologia , Antibacterianos , Anti-Infecciosos/farmacologia , Antifúngicos/farmacologia , Bactérias/efeitos dos fármacos , Fungos/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade MicrobianaRESUMO
A set of substituted 1,3,4-triaryl-2-azetidinones were synthesized and characterized. Their antimicrobial activity, against Gram+ and Gram- bacteria and Fungi, was tested. The compounds 23 and 30 showed remarkable activity against Pseudomonas aeruginosa.
Assuntos
Anti-Infecciosos/síntese química , Azetidinas/síntese química , Antibacterianos , Anti-Infecciosos/farmacologia , Azetidinas/farmacologia , Fungos/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
A series of aryl-hydroxy-piperidinoalkyl-thiazolidinones was synthesized and evaluated to inhibit castor oil-induced diarrhea in mice. The dose dependent antidiarrheal activity of the most active compound 2-(p-nitrophenyl)-3-¿2-[(4-(p-chlorophenyl)-4-hydroxy)piperidino]ethyl]- 1, 3-thiazolidin-4-one (6) was counteracted by naloxone, resulting comparable with that of loperamide, a mu opiate agonist.
Assuntos
Antidiarreicos/farmacologia , Piperidinas/farmacologia , Tiazóis/farmacologia , Animais , Antidiarreicos/síntese química , Masculino , Camundongos , Estrutura Molecular , Piperidinas/síntese química , Tiazóis/síntese químicaRESUMO
2-(Substituted-phenyl)-3-[3-(N,N-dimethylamino)propyl]-1,3-thiazolidi n-4- ones (1-15) showed dependence of the potency of the H1-histamine antagonism on the m- and p-substituents suggesting that the aromatic moiety binds the receptor by a strong pi-interaction. Electron-withdrawing substituents decrease the potency while the electron-donating alkyl substituents, enhancing the aryl HOMO energy, increase the antihistamine activity. The m-substituents with the capability to form hydrogen bonds, seems to share an extra-interaction with hydrogen accepting or donating groups of the histamine receptor and exhibits very high potency.
Assuntos
Antagonistas dos Receptores Histamínicos H1/síntese química , Antagonistas dos Receptores Histamínicos H1/farmacologia , Tiazóis/síntese química , Tiazóis/farmacologia , Antagonistas dos Receptores Histamínicos H1/química , Espectroscopia de Ressonância Magnética , Relação Estrutura-Atividade , Tiazóis/químicaAssuntos
Anti-Infecciosos/síntese química , Indóis/síntese química , Compostos de Espiro/síntese química , Antibacterianos , Anti-Infecciosos/farmacologia , Antifúngicos/síntese química , Antifúngicos/farmacologia , Fungos/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Indóis/farmacologia , Testes de Sensibilidade Microbiana , Compostos de Espiro/farmacologiaRESUMO
The following 2-substituted phenyl-3-(N,N-dimethylaminopropyl)-1,3-thiazolidin-4-one of general formula (A): [formula: see text] where: X = H (I), 3-F (II), 3-Cl (III), 3-Br (IV), 3-CH3 (V), 3-OCH3 (VI), 3-NO2 (VII), 4-F (VIII), 4-Cl (IX), 4-Br (X), 4-CH3 (XI), 4-OCH3 (XII), 4-NO2 (XIII) were prepared and tested for antihistamine activity. The synthetic procedure involves the cyclocondensation of the appropriate Schiff base with thioglycolic acid in refluxing dry benzene. The compounds herein presented were tested for their ability to inhibit the contraction inducted by histamine 5.10(-7) M "in vitro", on guinea pig ileum. The results are reported as contraction of test compound causing 50% of submaximal contraction induced by histamine (IC50), and related to mepyramine as control. The results of the antihistamine tests showed an interesting degree of activity of some of the new thiazolidinone-derivatives. Compounds II, III, V, X, and XI showed IC50 values near the value of the control, compound XI being the most active. These compounds seem to be worthy of further investigation.
Assuntos
Antagonistas dos Receptores Histamínicos/síntese química , Tiazóis/farmacologia , Animais , Feminino , Cobaias , Histamina/farmacologia , Antagonistas dos Receptores Histamínicos/química , Antagonistas dos Receptores Histamínicos/farmacologia , Íleo/efeitos dos fármacos , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Pirilamina/farmacologia , Bases de Schiff , Relação Estrutura-Atividade , TiazolidinasRESUMO
The following halogenated 3'-phenyl [3H-indole-3,2'-thiazolidine]-2,4'(1H)-dione of general formula (A) were synthesized and screened for antimicrobial activity. (formula: see text) where: X = H (I, III, V, VII, IX, XI, XIII, XV), CH3 (II, IV, VI, VIII, X, XII, XIV, XVI); Y = H (I, II), 3-F (III, IV), 2-Cl (V, VI), 3-Cl (VII, VIII), 4-Cl (IX, X), 2-Br (XI, XII), 3-Br (XIII, XIV), 4-Br (XV, XVI). The synthetic approach involves the preparation of variously substituted Schiff-bases of indol-2,3-dione, which then are subjected to cyclocondensation with alpha-mercaptoalkanoic acids, to give spirothiazolidinones of type (A). The prepared compounds were screened against S. aureus, B. cereus, M. paratuberculosis, E. coli, S. typhi, Pr. mirabilis, Ps. aeruginosa, C. albicans, S. cerevisiae, A. niger by a disk-diffusion assay (Kirby-Bauer modified. The results of the antimicrobial screening showed that the prepared compounds exhibited varying degrees of activity against Gram-positive, Gram-negative bacteria, and fungi. 3-Fluoro-derivative (III) showed inhibitory activity especially toward S. aureus and C. albicans. Chloroderivatives (VII) and (VIII) showed broad-spectrum "in vitro" antimicrobial activity, and were especially inhibitory toward S. aureus, E. coli, and S. Typhi. Fluoro-derivative (IV) and bromo-derivatives (XIII) and (XIV) possessed marked antimicrobial activity against M. paratuberculosis.
Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Compostos de Espiro/farmacologia , Tiazóis/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Bactérias/efeitos dos fármacos , Fungos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Compostos de Espiro/síntese química , Compostos de Espiro/química , Relação Estrutura-Atividade , Tiazóis/síntese química , Tiazóis/químicaRESUMO
The following polyhalogenated 3'-phenyl 3H-indole-3,2'-thiazolidine -2,4' (1H)-dione of general formula (A) were synthesized and screened for antimicrobial activity. (formula: see text) where: X = H (I, III, V, VII, IX, XI), CH3 (II, IV, VI, VIII, X, XII); Y = H (I, II), 2,4-F2 (III, IV), 2,4-Cl2 (V, VI), 3,4-Cl2 (VII, VIII), 2,6-Cl2 (IX, X), 2,4,6-Cl3 (XI, XII). The general synthetic route involves the preparation of variously substituted isatin-3-imines, which are subjected to cyclocondensation with thioglycolic acid to give compounds I, III, V, VII, IX, XI, or thiolactic acid to give compounds II, IV, VI, VII, X, XII. The prepared compounds were screened against S. aureus, B. cereus, M. paratuberculosis, E. coli, Pr. mirabilis, Ps. aeruginosa, C. albicans, S. cerevisiae, A. niger by a disk-diffusion assay (Kirby-Bauer modified). The results of the antimicrobial screening showed that the polyhalogenated derivatives of type (A) exhibited varying degrees of activity against Gram-positive, Gram-negative bacteria, and fungi. Compound (III) showed a significant activity toward A. niger, moreover compound (IV) was active toward C. albicans. Compound (IX) was very active toward S. typhi and Ps. aeruginosa. Compounds (VII), (IX) and (XII) were very active toward M. paratuberculosis.
Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Compostos de Espiro/farmacologia , Tiazóis/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Bactérias/efeitos dos fármacos , Fungos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Compostos de Espiro/síntese química , Compostos de Espiro/química , Relação Estrutura-Atividade , Tiazóis/síntese química , Tiazóis/químicaRESUMO
The following 2,3-diaryl-1,3-thiazolidin-4-ones of general formula (A) were synthesized and screened for antimicrobial activity. (formula; see text) where: X = H (I, III, V, VII, IX, XI, XIII, XV, XVII, XIX, XXI, XXIII), CH3 (II, IV, VI, VIII, X, XII, XIV, XVI, XVIII, XX, XXII, XXIV); R = H (I, II, V, VI, VII, VIII, XI, XIII), 4-CH3 (XXI, XXII, XXIII, XXIV), 4-Br (III, IV, IX, X), 2-NO2 (XIII, XIV), 3-NO2 (XV, XVI), 4-NO2 (XVII, XVIII), 4-OCH3 (XIX, XX); R' = H (I, II, III, IV, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII), 4-CH3 (XXIII, XXIV), 3-Br (V, VI), 4-Br (VII, VIII, IX, X), 4-J (XI, XII). These compounds were prepared by the general synthetic procedure previously reported for the 1,3-thiazolidin-4-one derivatives already prepared and screened in this SARs program. The synthetic approach involves the cyclocondensation of the appropriate Schiff bases with alpha-mercaptoalkanoic acids. The prepared compounds were screened against S. aureus, S. beta-haemolititicus, B. subtilis, M. paratuberculosis 607, S. typhi, Kl. pneumoniae, E. coli Bb, Ps, aeruginosa, C. albicans, A. niger, S. cerevisiae by a disk-diffusion assay (Kirby-Bauer modified). The results obtained in this investigation showed that the prepared compounds exhibited varying degrees of antimicrobial activity. They were especially inhibitory toward Gram-positive bacteria, and fungi. 4-Nitroderivatives (XVII), (XVIII), and 2-nitroderivatives (XIV) and (XIII) possessed marked antimicrobial activity against S. aureus, S. beta-haemoliticus, and B. subtilis.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Bactérias/efeitos dos fármacos , Fungos/efeitos dos fármacos , Tiazóis/farmacologia , Testes de Sensibilidade Microbiana , Relação Estrutura-AtividadeRESUMO
A series of 2-(3- and 4-substituted phenyl)-3-[3-(N, N-dimethyl-amino)propyl]-1,3-thiazolidin-4-ones acting as H1-antihistaminics was investigated with a combined Hansch-CoMFA approach. The substituents at the 3- and 4-positions of the phenyl ring have been described through steric, electronic and hydrophobic parameters and correlated with pA2 values. The obtained quantitative models suggest that affinity to the receptor is promoted by hydrophobic and small 4-substituents and by 3- and 4-substituents generating a positive electrostatic potential towards a complementary receptor region.
Assuntos
Antagonistas dos Receptores Histamínicos H1/química , Antagonistas dos Receptores Histamínicos H1/farmacologia , Tiazóis/química , Tiazóis/farmacologia , Animais , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Eletroquímica , Cobaias , Íleo/efeitos dos fármacos , Técnicas In Vitro , Modelos Moleculares , Relação Estrutura-AtividadeRESUMO
In previous communications from these laboratories, thiazolidinone derivatives of general formula (A) were synthesized and screened for antimicrobial activity. (formula; see text) where: X = H, CH3 Ar = phenyl Ar' = fluorinated or chlorinated phenyl The present communication is in part concerned with further extension of these studies to variously halogenated thiazolidinones of general formula (B). (formula; see text) where: X = H, CH3 R = H, 2-F, 3-F, 4-F, 3-Cl, 4-Cl R' = H, 4-F, 4-Cl These compounds were prepared by the general synthetic procedure previously reported for the 1,3-thiazolidin-4-one derivatives already prepared and screened in this SARs program. The general synthetic approach involves the cyclocondensation of the appropriate Schiff bases with alpha-mercaptoalkanoic acids such as thioglycolic and thiolactic acid. The prepared compounds were tested for their possible activity by a disk-diffusion assay (Kirby-Bauer modified). The organisms used were: S. aureus, S. beta-haemoliticus, B. subtilis, M. paratuberculosis 607, S. typhi, Kl. pneumoniae, E. coli Bb, Ps. aeruginosa, C. albicans, A. niger, S. cerevisiae. The results of this antimicrobial screening showed that the prepared compounds exhibited varying degrees of activity against Gram-positive, Gram-negative bacteria, and fungi. The second half of this report deals with the structure-activity relationships in all the compounds prepared and studied in this research program. For comparison of antimicrobial activity, the growth inhibitory activity of all the halogenated thiazolidinones of type (A) and (B), prepared and screened in this SARs study, were tabulated.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Bactérias/efeitos dos fármacos , Fungos/efeitos dos fármacos , Tiazóis/farmacologia , Halogênios , Testes de Sensibilidade MicrobianaRESUMO
The following hydrazono derivatives (I-XXIII) of type (A), (formula; see text) where: X = NO2 (II, IV, VI, VIII, X, XIV-XXIII), X = H (I, III, V, VII, IX, XI, XII, XIII), and Y = H (I, II); 3-Cl (III, IV); 4-Cl (V, VI); 3,4-Cl2 (VII, VIII); 2,6-Cl2 (IX, X); 2-NO2 (XI); 3-NO2 (XII); 4-NO2 (XIII, XIV); 2-F (XV); 3-F (XVI); 4-F (XVII); 2-OH (XVIII); 4-OH (XIX); 2,4-(OH)2(XX); 2,4,6-(OH)3(XXI); 2,3-(OH,NO2) (XXII); 2,4-(NO2)2 (XXIII), were prepared and tested for antibacterial and antifungal activity. All of these compounds were prepared in satisfactory yield by reaction of aromatic aldehydes with 2-furoyl and 5-nitro-2-furoyl hydrazide. The hydrazono derivatives I-XXIII prepared in this investigation were screened for antimicrobial activity by a disk-diffusion assay (Kirby-Bauer modified). The organisms used were laboratory cultures of S. aureus, S. -haemoliticus, B. subtilis, M. paratuberculosis, E. coli, S. typhi, Ps. aeruginosa, K1. pneumoniae, A. niger, S. cerevisiae, C. albicans. The results of this study showed that a number of the prepared hydrazono derivatives exhibited varying degrees of activity against Gram-positive and Gram-negative bacteria. Compounds IV and XV possessed broad spectrum "in vitro" against Gram-positive and Gram-negative bacteria. Compounds XII greater than IV greater than XV showed inhibitory activity especially toward S. aureus. Compounds IV greater than XV greater than XVI were especially active against E. coli. Compounds XV greater than IV were especially inhibitory toward S. typhi and most of the prepared compounds inhibited considerably Ps. aeruginosa and K1. pneumoniae.
Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Hidrazonas/farmacologia , Antibacterianos/síntese química , Hidrazonas/síntese química , Testes de Sensibilidade Microbiana , Relação Estrutura-AtividadeRESUMO
3,4-Dihydroxyphenylethanol (DOPET) is the major o-diphenol detectable in extra virgin olive oil, either in free or esterified form. Despite its relevant biological effects, mainly related to its antioxidant properties, little data have been reported so far on its toxicity and metabolism. The aim of the present work is to evaluate DOPET toxicity and to investigate its molecular pharmacokinetics by using the (14)C-labeled diphenol. When orally administered to rats, the molecule does not show appreciable toxicity up to 2 g/kg b.wt. To identify and quantify its metabolites, [(14)C]DOPET has been synthesized and intravenously injected in rats. The pharmacokinetic analysis indicates a fast and extensive uptake of the molecule by the organs and tissues investigated, with a preferential renal uptake. Moreover, 90% of the administered radioactivity is excreted in urine collected up to 5 h after injection, and about 5% is detectable in feces and gastrointestinal content. The characterization of the labeled metabolites, extracted from the organs and urine, has been performed by high-pressure liquid chromatography analysis. In all the investigated tissues, DOPET is enzymatically converted in four oxidized and/or methylated derivatives. Moreover, a significant fraction of total radioactivity is associated with the sulfo-conjugated forms, which also represent the major urinary excretion products. On the basis of the reported results, an intracellular metabolic pathway of exogenously administered DOPET, implying the involvement of catechol-O-methyltransferase, alcohol dehydrogenase, aldehyde dehydrogenase, and phenolsulfotransferase, has been proposed.