Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 12 de 12
Filter
Add more filters










Publication year range
1.
Arch Med Sci ; 18(6): 1467-1474, 2022.
Article in English | MEDLINE | ID: mdl-36457982

ABSTRACT

Introduction: The current study was designed to analyze whether polymorphisms of miR-146a and miR-155 are related to Behçet's disease (BD) in the Egyptian population. Material and methods: A total of 96 unrelated BD patients and 100 healthy subjects were genotyped for miR-146a (rs2910164) and miR-155 (rs767649) using real-time polymerase chain reaction. Results: The results showed significant elevation in the frequency of rs2910164 GG and CC genotypes in BD patients compared with controls (adjusted OR = 22.156, 95% CI: 4.728-103.818; p < 0.001 and adjusted OR = 40.358, 95% CI: 8.928-182.440; p < 0.001, respectively). Also, the rs2910164 G allele conferred a higher risk of developing BD (adjusted OR = 3.665, 95% CI: 2.013-6.671; p < 0.001). MiR-146a (rs2910164) polymorphism was a risk factor for susceptibility to BD in dominant, recessive and additive models of inheritance (all p < 0.001), while the miR-155 (rs767649) polymorphism was a risk factor in the recessive model only (p = 0.021). GG and CG genotypes of rs2910164 were associated with higher Behcet's disease current activity index (BDCAI) and ocular involvement compared with CC genotype (p = 0.005 and p = 0.004, respectively). Genotype AT of rs767649 was related to higher BDCAI (p = 0.026) compared with TT and AA genotypes. Conclusions: miR-146a (rs2910164) and miR-155 (rs767649) are likely to play an important role in the Egyptian population in development of BD and also influence disease severity.

2.
PLoS One ; 17(8): e0268176, 2022.
Article in English | MEDLINE | ID: mdl-35972968

ABSTRACT

BACKGROUND: The role of the long non-coding RNAs (lncRNAs) in the pathogenesis of systemic lupus erythematosus (SLE) is mostly unknown, despite increasing evidence that lncRNAs extensively participate in physiological and pathological conditions. AIM: To detect the level of lncRNA-Cox2, HOTAIR, IL-6, and MMP-9 in the serum of SLE patients and to correlate these levels with disease activity and patients' clinical and laboratory data to evaluate the value of these biomarkers for SLE diagnosis and assessment of disease activity. METHODS: Blood samples from 58 SLE patients, and 60 healthy controls (HCs) were used for detection of lncRNAs-Cox2 and HOTAIR expression levels by real-time polymerase chain reaction. Both IL-6 and MMP-9 serum levels were assayed by enzyme-linked immunosorbent assay. Lupus activity was assessed with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). RESULTS: The serum expression levels of lncRNA-Cox2 and HOTAIR were significantly up-regulated in SLE patients vs HCs (fold change [median (IQR) was 1.29(0.81-1.71, P<0.0001) and 2.68(0.95-3.67), P = 0.038) for lncRNA-Cox2 and HOTAIR, respectively. Serum levels of both IL-6 and MMP-9 were significantly high in SLE patients compared with HCs (P≤0.001 for each). The up-regulated lncRNA-Cox2 was positively associated with the presence of neurological manifestations in SLE patients (P = 0.007). Furthermore, HOTAIR expression level had significantly positive correlation with IL-6 (r = 0.578, P<0.0001), MMP-9 level (r = 0.762, P<0.0001), nephritis grades (r = 0.296, P = 0.024) and proteinuria (r = 0.287, P = 0.035). LncRNA-Cox2 showed sensitivity and specificity 72.4%, and 100.0% respectively. HOTAIR sensitivity was 60.3%, and specificity was 100.0%. By multiple logistic regression analysis, lncRNA-Cox2 and HOTAIR were found as SLE independent predictors. CONCLUSION: LncRNA-COX2 and HOTAIR can be used as new non-invasive biomarkers for the diagnosis of SLE.


Subject(s)
Lupus Erythematosus, Systemic , Lupus Nephritis , RNA, Long Noncoding , Biomarkers , Humans , Interleukin-6/blood , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/genetics , Matrix Metalloproteinase 9/blood , RNA, Long Noncoding/genetics
3.
Med Chem ; 17(7): 707-723, 2021.
Article in English | MEDLINE | ID: mdl-32250227

ABSTRACT

BACKGROUND: Previous and recent scientific research has shown that triazolopyrimidine and furochromones have a wide range of pharmacological activities for the treatment of numerous diseases, including anticancer, antiviral, anti-depressant, anti-microbial, anti-inflammatory, and analgesic activities. OBJECTIVE: Preparation of new drugs derived from a natural furochromones as (1-hydrazinyl or methylthio),-furopyrimidoquinazolinone, 1, 2, 4-triazolopyrimidofuroquinazolin-5-one, and quinazoline- pyrimidofuro- quinazoline-8, 10-dione and the study of their biological activity as antimicrobial agents. METHODS: A series of novel N'-furopyrimidoquinazoline-hydrazide; 1, 2, 4-triazolopyrimidofuroquinazolin- 5-one; furopyrimidoquinazolin-3-one and quinazoline-pyrimidofuroquinazoline-8, 10- dione derivatives were synthesized from substituted (methylthio)-furopyrimidoquinazolinone (3ab) and 1-hydrazinyl-furopyrimido- quinazolinone (4a-b) as the starting material. RESULTS: All compounds were synthesized in good yields (71-95%) in a gradually efficient system under mild condition and some of the procedures were used such as microwave oven. The new compounds have been confirmed by means of different spectroscopic methods such as IR, 1D and 2D -NMR techniques and mass spectrum. The in vitro antimicrobial activities were evaluated for the prepared compounds using many types of bacteria (Gram-positive and Gram-negative) and fungi. CONCLUSION: 1, 2, 4-triazolopyrimidofuroquinazolin-5-one derivatives (10a-f, 8a-b, 7a-b and 6a-d) showed the most efficient antimicrobial activities compared with the cefotaxime sodium and nystatin as standard drugs.


Subject(s)
Anti-Infective Agents/chemical synthesis , Anti-Infective Agents/pharmacology , Benzofurans/chemistry , Quinazolinones/chemical synthesis , Quinazolinones/pharmacology , Anti-Infective Agents/chemistry , Chemistry Techniques, Synthetic , Microbial Sensitivity Tests , Quinazolinones/chemistry , Structure-Activity Relationship
4.
J Interferon Cytokine Res ; 39(3): 174-180, 2019 03.
Article in English | MEDLINE | ID: mdl-30668267

ABSTRACT

Despite the increased proof that long noncoding RNAs (lncRNAs) can control gene expression and broadly affect the normal physiological and disease conditions, the part of lncRNAs in rheumatoid arthritis (RA) is not well known. This study aimed to assess the serum expression levels of lnc-Cox2 and HOTAIR in RA and to investigate their role as novel noninvasive biomarkers in diagnosis of RA. Also, their relations with the levels of interleukin (IL)-6 and matrix metalloproteinase (MMP)-9 and with other clinicolaboratory data in RA patients were analyzed. LncRNAs-Cox2 and HOTAIR expression levels were detected in serum by real-time quantitative polymerase chain reaction. Both IL-6 and MMP-9 levels in serum were measured by enzyme-linked immunosorbent assay. The mRNA expression of lncRNA-Cox2 and HOTAIR was significantly upregulated in RA patients compared with healthy controls. Serum levels of both IL-6 and MMP-9 were significantly higher in RA patients than in healthy subjects (P < 0.001 each). Receiver operating characteristic (ROC) curve demonstrated that lncRNA-Cox2 and HOTAIR could discriminate RA patients from healthy controls. HOTAIR (not lnc-Cox2) was observed to be an independent predictor for RA using multiple logistic regression analysis. We concluded that lnc-Cox2 and HOTAIR serum expression levels can be used as novel noninvasive biomarkers for the diagnosis of RA.


Subject(s)
Arthritis, Rheumatoid/genetics , Cyclooxygenase 2/genetics , RNA, Long Noncoding/genetics , Adult , Arthritis, Rheumatoid/blood , Biomarkers/blood , Cyclooxygenase 2/blood , Female , Gene Expression Profiling , Humans , Interleukin-6/blood , Male , Matrix Metalloproteinase 9/blood , RNA, Long Noncoding/blood
5.
Innov Clin Neurosci ; 15(9-10): 25-29, 2018 Oct 01.
Article in English | MEDLINE | ID: mdl-30588363

ABSTRACT

Objective: Neurocognitive impairment is one of the most common systemic lupus erythematosus (SLE) manifestations. However, its pathophysiology is still poorly understood. Vitamin D deficiency is a possible risk factor for cognitive impairment. The aim of this study was to evaluate the relationship between 25-dihydroxy(OH) D3 levels and cognitive performance in patients with SLE. Methods: This was a cross-sectional, case-control study that included 30 Egyptian patients diagnosed with SLE and 20 age, sex, and educational level-matched controls. Study participants were subjected to a battery of neuropsychological evaluation using the California Verbal Learning Test (CVLT- II), Controlled Oral Word Association Test (COWAT), and Trail Making Test and evaluation of depression using Beck Depression Inventory (BDI). Serum levels of 25(OH) D3 were measured in the SLE group and control group. Results: The patients with SLE performed worse on total recall of verbal memory and executive function tests than the healthy controls. There was no significant difference between the patients and controls in Beck Depression Inventory (BDI). There was a significant negative correlation between vitamin D levels and executive function assessed by Trail Making Test (r=-0.399, p=0.03). Conclusion: Vitamin D deficiency could have a significant impact on cognitive performance in patients with SLE.

6.
Bioorg Chem ; 78: 312-323, 2018 08.
Article in English | MEDLINE | ID: mdl-29625271

ABSTRACT

Tyrosine kinases are one of the most critical mediators in the signaling path way. Late studies have proved the part of tyrosine kinases in the pathophysiology of cancer diseases. This current research paper has focused on investigating the novel Pyrazolo[1,5-a]pyrimidines and Pyrido[2,3-d]pyrimidines as a small molecules that can inhibit tyrosine kinase in cancer cells. NCI protocol was applied to test the antitumor activity of such compounds. Leukemia and renal cancer cell lines proved to be sensitive to some derivatives such as 6b-d, 9a and 11 with GI% values ranging from 30.4 to 41.3%. In addition, compound 11 proved to be the most active against MCF-7 with GI% 62.5. The synthesized compounds were also evaluated for their inhibitory effects against EGFR kinase enzyme. Compound 9b proved to be the most active one among the synthesized series with inhibition % value of 81.72 at 25 nM concentration and IC50 8.4 nM which is very close to the reference drug Sorafenib. In vitro cytotoxicity test was also performed using the MCF-7 breast cell line. Computer modeling using the active site of tyrosine kinase as a template and the most active tyrosine kinase inhibitors were calculated. Docking studies of the synthesized compounds into the active site of EGFR kinase domain showed good agreement with the obtained biological results.


Subject(s)
Antineoplastic Agents/pharmacology , Protein Kinase Inhibitors/pharmacology , Protein-Tyrosine Kinases/antagonists & inhibitors , Pyrazoles/pharmacology , Pyridines/pharmacology , Pyrimidines/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Ligands , Models, Molecular , Molecular Structure , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Protein-Tyrosine Kinases/metabolism , Pyrazoles/chemical synthesis , Pyrazoles/chemistry , Pyridines/chemical synthesis , Pyridines/chemistry , Pyrimidines/chemical synthesis , Pyrimidines/chemistry , Structure-Activity Relationship
7.
Nucleosides Nucleotides Nucleic Acids ; 36(7): 474-495, 2017 Jul 03.
Article in English | MEDLINE | ID: mdl-28613111

ABSTRACT

New [(Indolyl)pyrazolyl]-1,3,4-oxadiazole compounds and their derived thioglycosides as well as the corresponding sugar hydrazones were synthesized. The acyclo C-nucleoside analogs of the oxadiazoline base system were also prepared by reaction of acid hydrazides with aldehydo sugars followed by one pot process encompassing acetylation and cyclization of the synthesized hydrazones. The anticancer activity of the newly synthesized compounds was studied against colorectal carcinoma (HCT116), breast adenocarcinoma (MCF7) and prostate cancer (PC3) human tumor cell lines and a number of compounds showed moderate to high activities.


Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Nucleosides/chemistry , Oxadiazoles/chemistry , Thioglycosides/chemical synthesis , Thioglycosides/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Catalytic Domain , Cell Line, Tumor , Cyclin-Dependent Kinase 2/chemistry , Cyclin-Dependent Kinase 2/metabolism , Cyclization , Humans , Molecular Docking Simulation , Structure-Activity Relationship , Thioglycosides/chemistry , Thioglycosides/metabolism
8.
Nucleosides Nucleotides Nucleic Acids ; 36(3): 213-223, 2017 Mar 04.
Article in English | MEDLINE | ID: mdl-28102765

ABSTRACT

A convenient method for the regioselective synthesis of pyrimidine non-nucleoside analogs was developed. This study reports a novel and efficient method for the synthesis of a new type of N-substituted amino methylsulfanylpyrimidines and the corresponding pyrazolo[3,4-d]pyrimidines. This series of compounds was designed through the reaction of dimethyl N-cyanodithioiminocarbonate with 2-cyano-N'-(thiophen-2-yl-, furan-2-yl- and pyridin-4-ylmethylene)acetohydrazide and N'-(2-cyanoacetyl)arylsulfonohydrazides. The scope and limitation of the method are demonstrated. The antibacterial and antifungal activities of the synthesized compounds were also evaluated.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Pyrimidines/chemical synthesis , Sulfonamides/chemistry , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Chemistry Techniques, Synthetic , Drug Evaluation, Preclinical/methods , Molecular Structure
9.
Nucleosides Nucleotides Nucleic Acids ; 36(2): 139-150, 2017 Feb.
Article in English | MEDLINE | ID: mdl-28045647

ABSTRACT

The synthesis of a new category of novel cytosine 4-thioglycoside analogs has been first accomplished. The main step of this strategy is the synthesis of sodium pyrimidine-4-thiolate through the condensation of 2-cyano-N-arylacetamides with sodium cyanocarbonimidodithioate, followed by coupling with α-bromo-sugars to afford the corresponding cytosine 4-thioglycoside analogs. The free thioglycosides were also prepared. Subsequent studies on the application of this strategy for the preparation of other potent pyrimidine thioglycosides are reported.


Subject(s)
Cytosine/chemistry , Thioglycosides/chemical synthesis , Chemistry Techniques, Synthetic , Drug Design , Molecular Structure
10.
Acta Crystallogr E Crystallogr Commun ; 71(Pt 11): 1322-4, 2015 Nov 01.
Article in English | MEDLINE | ID: mdl-26594501

ABSTRACT

The title compound, C12H10BrN5O3S2·C3H7NO, displays an almost planar amine group. The inter-planar angle between the rings is 31.72 (6)°. The residues are associated into ribbons parallel to [110] by three classical hydrogen bonds; one from each amine Hamine to ODMF and one from NHamide to Ooxo. Adjacent ribbons are connected by translation parallel to the c axis by a 'weak' hydrogen bond Hmeth-yl⋯Osulfon-yl to form a layer structure parallel to (1-10), while a further contact Hbromo-phen-yl⋯Osulfon-yl connects the residues in the third dimension.

11.
Eur J Med Chem ; 45(9): 4026-34, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20691339

ABSTRACT

Previously, we synthesized and evaluated several thienopyrimidine derivatives containing heterocyclic ring substituents linked to the pyrimidine-2-thione nucleus at C-2 by a two- to four-atom spacer as potential anti-HIV-1 and antimicrobial agents. Also, from the literature, S-substituted pyrimidin-4-ones A and B exhibited interesting anti-HIV-1 activity. To further investigate the synthesis, tools and biological activities, we synthesized several new thienopyrimidine derivatives derived from thieno[2,3-d]-pyrimidine-2,4-dithione (3a,b) The compounds were designed to comprise the heterocyclic substituents directly linked to the thienopyrimidines nucleus at C-2. Moreover, various related triazolo[4,3-a]benzothieno[2,3-d]pyrimidines derived from 2-thioxothienopyrimidine were also prepared as isosteres. Among the synthesized derivatives 3-18, the compounds 3a, 8a, 10a, 13a and 14a were showing complete inhibition at 128 mg/mL or less.


Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Glycosides/chemistry , Pyrimidines/chemistry , Pyrimidines/pharmacology , Anti-Bacterial Agents/chemical synthesis , Antiviral Agents/chemical synthesis , Bacteria/drug effects , HIV-1/drug effects , Herpesvirus 1, Human/drug effects , Inhibitory Concentration 50 , Pyrimidines/chemical synthesis
12.
Acta Pharm ; 57(4): 395-411, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18165185

ABSTRACT

5-Methyl-6-phenyl-2-thioxothieno[2,3-d]pyrimidone derivative (2) reacted with hydrazonoyl chloride derivatives to afford triazolothienopyrimidones 4a-f. Also, acetone-1-(2-amino-5-isopropyl-thiophene-3-carbonitrile) (3) reacted with functional and bifunctional groups to yield the corresponding compounds 5-11. The new products showed anti-inflammatory, analgesic, and ulcerogenic activities comparable to that of indomethacin and acetylsalicylic acid, respectively.


Subject(s)
Analgesics , Anti-Inflammatory Agents , Inflammation/prevention & control , Pain/prevention & control , Pyridines , Stomach Ulcer/chemically induced , Acetic Acid , Analgesics/chemical synthesis , Analgesics/pharmacology , Analgesics/toxicity , Animals , Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/toxicity , Aspirin/pharmacology , Carrageenan , Disease Models, Animal , Female , Indomethacin/pharmacology , Inflammation/chemically induced , Male , Mice , Molecular Structure , Pain/chemically induced , Pain/physiopathology , Pain Measurement , Pain Threshold/drug effects , Pyridines/chemical synthesis , Pyridines/pharmacology , Pyridines/toxicity , Rats , Stomach Ulcer/pathology , Structure-Activity Relationship
SELECTION OF CITATIONS
SEARCH DETAIL
...