ABSTRACT
Several studies have demonstrated that allelic variants related to inflammation and the immune system may increase the risk for major depressive disorder (MDD) and reduce patient responsiveness to antidepressant treatment. Proteasomes are fundamental complexes that contribute to the regulation of T-cell function. Only one study has shown a putative role of proteasomal PSMA7, PSMD9 and PSMD13 genes in the susceptibility to an antidepressant response, and sparse data are available regarding the potential alterations in proteasome expression in psychiatric disorders such as MDD. The aim of this study was to clarify the role of these genes in the mechanisms underlying the response/resistance to MDD treatment. We performed a case-control association study on 621 MDD patients, of whom 390 were classified as treatment-resistant depression (TRD), and we collected peripheral blood cells and fibroblasts for mRNA expression analyses. The analyses showed that subjects carrying the homozygous GG genotype of PSMD13 rs3817629 had a twofold greater risk of developing TRD and exhibited a lower PSMD13 mRNA level in fibroblasts than subjects carrying the A allele. In addition, we found a positive association between PSMD9 rs1043307 and the presence of anxiety disorders in comorbidity with MDD, although this result was not significant following correction for multiple comparisons. In conclusion, by confirming the involvement of PSMD13 in the MDD treatment response, our data corroborate the hypothesis that the dysregulation of the complex responsible for the degradation of intracellular proteins and potentially controlling autoimmunity- and immune tolerance-related processes may be involved in several phenotypes, including the TRD.
Subject(s)
Depressive Disorder, Major/genetics , Depressive Disorder, Treatment-Resistant/genetics , Proteasome Endopeptidase Complex/genetics , Case-Control Studies , Female , Humans , Male , Middle AgedABSTRACT
A series of 6-thioxopyrimidines (5, 6), their 6-oxo- analogs (11-14), and pyrimidine-2,4-diones (20-26), were synthesized and evaluated for their antitumoral activity against 60 tumoral cell lines. The activity of propenethioamide (3, 4) and propeneamide (7-10 and 15-19) intermediates is also reported. Among the tested compounds the thioxopyrimidine 5c, bearing an N'-benzyl group, showed the best cytostatic activity. Furthermore, high selectivity and cytotoxic activity on the HOP-92 cell line of non-small cell lung cancer was exhibited by 3-amino-2-[(methylamino)thioxamethyl]-3-pyrrolidino-2-propenenitrile (3a).
Subject(s)
Antineoplastic Agents/chemical synthesis , Neoplasms/drug therapy , Pyrimidines/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , Chemistry, Pharmaceutical , Humans , Pyrimidines/chemistry , Pyrimidines/therapeutic use , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
4-hydroxy-2-pyridone derivatives 2 were prepared by reaction of 3-amino-3-dialkylaminopropenoates with bis(2,4, 6-trichlorophenyl)malonate. These compounds were further reacted with a set of aldehydes to give bis(pyridyl)methanes 3 and 4. The newly synthesized compounds 2, 3 and 4 were evaluated in vitro as antitumour agents against 60 human tumour cell lines. Some derivatives exhibit tumour growth inhibition activity. In particular, derivative 4g, the most active of the series, possesses significant activity on all cell lines at concentrations ranging from 1 x 10(-6) to 1 x 10(-5) M.
Subject(s)
Antineoplastic Agents/chemical synthesis , Morpholines/chemical synthesis , Pyridones/chemical synthesis , Antineoplastic Agents/pharmacology , Humans , Molecular Structure , Morpholines/pharmacology , Pyridines/chemistry , Pyridones/pharmacology , Tumor Cells, CulturedABSTRACT
A convenient and simple synthesis of some new thioxopyrimidines was developed starting from 3-amino-3-(dialkylamino)propenethioamide derivatives. The prepared compounds were assayed in vitro for antimicrobial activity and found practically inactive.
Subject(s)
Anti-Infective Agents/chemical synthesis , Pyrimidines/chemical synthesis , Anti-Bacterial Agents , Anti-Infective Agents/pharmacology , Bacteria/drug effects , Fungi/drug effects , Pyrimidines/pharmacologySubject(s)
Health Status Indicators , Mortality/trends , Adolescent , Adult , Age Distribution , Aged , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Italy/epidemiology , Male , Middle Aged , Sex Distribution , Vital StatisticsABSTRACT
The 3,5-diaminoisothiazole derivatives 23-42 were synthesized in excellent yields by oxidative cyclization of 3-amino-3-(dialkylamino)propenethioamide derivatives. These intermediates and the isothiazole derivatives were tested in vitro for their antimicrobial activity.
Subject(s)
Anti-Infective Agents/chemical synthesis , Thiazoles/chemical synthesis , Anti-Bacterial Agents , Anti-Infective Agents/pharmacology , Bacteria/drug effects , Fungi/drug effects , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Spectrophotometry, Infrared , Thiazoles/pharmacologySubject(s)
Bites and Stings/epidemiology , Cats , Dogs , Adolescent , Adult , Age Factors , Aged , Animals , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Italy/epidemiology , Male , Middle AgedABSTRACT
A new series of 1-arylideneamino-2-mercaptoimidazole derivatives obtained by condensation of 1-amino-2-mercaptoimidazole derivatives with variously substituted aromatic aldehydes is described. Investigation of their antimicrobial properties showed a good antibacterial activity for some of the tested compounds on some gram-positive micro-organisms.
Subject(s)
Anti-Infective Agents/chemical synthesis , Imidazoles/chemical synthesis , Anti-Bacterial Agents , Bacteria/drug effects , Chemical Phenomena , Chemistry , Fungi/drug effects , Imidazoles/pharmacology , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Spectrophotometry, InfraredABSTRACT
A new series of pyrrole derivatives obtained by heterocyclization of N1-aryliden-3-ethoxycarbonyl (or cyano) acetamidrazones with alpha-bromoketones was described. The in vitro microbiological investigation showed that none of the 2-arylidenhydrazinopyrrole derivatives presented any noteworthy activity.
Subject(s)
Anti-Infective Agents/chemical synthesis , Hydrazines/chemical synthesis , Pyrroles/chemical synthesis , Anti-Bacterial Agents , Anti-Infective Agents/pharmacology , Bacteria/drug effects , Chemical Phenomena , Chemistry , Fungi/drug effects , Hydrazines/pharmacology , Microbial Sensitivity Tests , Pyrroles/pharmacologyABSTRACT
The synthesis of 3-ethoxycarbonyl-5-aryl-pyrrole derivatives with an arylpiperazine group in position 2 is described. The in vitro biological investigation showed that compound (XVIII) had considerable antibacterial activity against gram-positive microorganisms and antifungal activity against Candida rugosa, while the other compounds did not show any significative activity.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Piperazines/chemical synthesis , Pyrroles/chemical synthesis , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Chemical Phenomena , Chemistry , Microbial Sensitivity Tests , Piperazines/pharmacology , Pyrroles/pharmacologyABSTRACT
A series of 2-(2'-acylhydrazino)-3-ethoxycarbonyl-3-aryl (or alkyl)-pyrrole derivatives was synthesized and submitted to in vitro microbiological screening. Most derivatives showed considerable antibacterial and antifungal activities.
Subject(s)
Anti-Infective Agents/chemical synthesis , Hydrazines/chemical synthesis , Pyrroles/chemical synthesis , Anti-Bacterial Agents , Anti-Infective Agents/pharmacology , Candida albicans/drug effects , Chemical Phenomena , Chemistry , Hydrazines/pharmacology , Magnetic Resonance Spectroscopy , Pyrroles/pharmacology , Staphylococcus aureus/drug effectsABSTRACT
The synthesis of some 5-substituted 2-amino-3-cyano (and 3-carboethoxy)pyrroles is described starting from the cyano- and carboethoxyacetomidines and the alpha-halogeno ketones. The compounds tested in vitro as antimicrobial agents did not show any significative activity.
Subject(s)
Anti-Infective Agents/chemical synthesis , Pyrroles/chemical synthesis , Anti-Bacterial Agents , Candida albicans/drug effects , Chemical Phenomena , Chemistry , Escherichia coli/drug effects , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Pyrroles/pharmacology , Staphylococcus aureus/drug effectsABSTRACT
The synthesis and microbiological activities of 1-arylideneaminoimidazole derivatives are reported. Antimicrobial data show that some of the tested imidazoles exhibited an interesting activity on Candida albicans.