Synthesis and biological evaluation of novel 2-morpholino-4-anilinoquinoline derivatives as antitumor agents against HepG2 cell line.

Cancer is a life-threatening illness all over the world, and developing anticancer treatments with high efficacy and low side effects remains a challenge. The quinoline ring structure has long been recognized as a flexible nucleus in the design and synthesis of physiologically active chemicals. In this study, five new 2-morpholino-4-anilinoquinoline compounds were synthesized and their biological anticancer potential against the HepG2 cell line was assessed. The compounds produced demonstrated varying responses against HepG2 cells, with compounds 3c, 3d, and 3e exhibiting the highest activity, with IC50 values of 11.42, 8.50, and 12.76 µM, respectively. It is a critical requirement that anticancer medications are able to selectively decrease cancer growth while not causing damage to normal cells. Compound 3e exhibited increased activity while maintaining adequate selectivity. It was also the most effective chemical against cell migration and adhesion, which could play an important role in drug resistance and cell metastasis. In total, the findings revealed good possibilities for anticancer therapy, suggesting a target for future development of anticancer medication.

Molecular Diversity via Tetrasubstituted Alkenes Containing a Barbiturate Motif: Synthesis and Biological Activity.

The synthesis of a molecularly diverse library of tetrasubstituted alkenes containing a barbiturate motif is described. Base-induced condensation of N1-substituted pyrimidine-2,4,6(1H,3H,5H)-triones with 5-(bis(methylthio)methylene)-2,2-dimethyl-1,3-dioxane-4,6-dione gave 3-substituted 5-(methylthio)-2H-pyrano[2,3-d]pyrimidine-2,4,7(1H,3H)-triones ('pyranopyrimidinones'), regioselectively. A sequence of reactions involving ring-opening of the pyran moiety, displacement of the methylthio group with an amine, re-formation of the pyran ring, and after its final cleavage with an amine, gave tetrasubstituted alkenes (3-amino-3-(2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene)propanamides) with a diversity of substituents. Cleavage of the pyranopyrimidinones with an aniline was facilitated in 2,2,2-trifluoroethanol under microwave irradiation. Compounds were tested against Escherichia coli, Staphylococcus aureus, the yeast Schizosaccharomyces pombe, and the pathogenic fungus Candida albicans. No compounds exhibited activity against E. coli, whilst one compound was weakly active against S. aureus. Three compounds were strongly active against S. pombe, but none was active against C. albicans.

Diurnal Changes in Water Soluble Carbohydrate Components in Leaves and Sucrose Associated TaSUT1 Gene Expression during Grain Development in Wheat.

In plant tissues, sugar levels are determined by the balance between sugar import, export, and sugar synthesis. So far, water soluble carbohydrate (WSC) dynamics have not been investigated in a diurnal context in wheat stems as compared to the dynamics in flag leaves during the terminal phases of grain filling. Here, we filled this research gap and tested the hypothesis that WSC dynamics interlink with gene expression of TaSUT1. The main stems and flag leaves of two genotypes, Westonia and Kauz, were sampled at four hourly intervals over a 24 h period at six developmental stages from heading to 28 DAA (days after anthesis). The total levels of WSC and WSC components were measured, and TaSUT1 gene expression was quantified at 21 DAA. On average, the total WSC and fructan levels in the stems were double those in the flag leaves. In both cultivars, diurnal patterns in the total WSC and sucrose were detected in leaves across all developmental stages, but not for the fructans 6-kestose and bifurcose. However, in stems, diurnal patterns of the total WSC and fructan were only found at anthesis in Kauz. The different levels of WSC and WSC components between Westonia and Kauz are likely associated with leaf chlorophyll levels and fructan degradation, especially 6-kestose degradation. High correlation between levels of TaSUT1 expression and sucrose in leaves indicated that TaSUT1 expression is likely to be influenced by the level of sucrose in leaves, and the combination of high levels of TaSUT1 expression and sucrose in Kauz may contribute to its high grain yield under well-watered conditions.

Contributions of TaSUTs to grain weight in wheat under drought.

KEY MESSAGE: The homologous genes to OsSUT1-5 in wheat were identified and detailed analysed. TaSUT1 was the predominant sucrose transporter group and it illustrated the genotypic variations towards drought during grain filling. Sucrose transporters (SUT) play crucial roles in wheat stem water soluble carbohydrate (WSC) remobilization to grain. To determine the major functional SUT gene groups in shoot parts of wheat during grain development, drought tolerant varieties, Westonia and Kauz, were investigated in field drought experiments. Fourteen homologous genes to OsSUT1-5 were identified on five homeologous groups, namely TaSUT1_4A, TaSUT1_4B, TaSUT1_4D; TaSUT2_5A, TaSUT2_5B, TaSUT2_5D; TaSUT3_1A, TaSUT3_1D; TaSUT4_6A, TaSUT4_6B, TaSUT4_6D; TaSUT5_2A, TaSUT5_2B, and TaSUT5_2D, and their gene structures were analysed. Wheat plants above the ground were harvested from pre-anthesis to grain maturity and the stem, leaf sheath, rachis, lemma and developing grain were used for analysing TaSUT gene expression. Grain weight, thousand grain weight, kernel number per spike, biomass and stem WSC were characterized. The study showed that among the five TaSUT groups, TaSUT1 was the predominant sucrose transporting group in all organs sampled, and the expression was particularly high in the developing grain. In contrast to TaSUT1, the gene expression levels of TaSUT2, TaSUT3 and TaSUT4 were lower, except for TaSUT3 which showed preferential expression in the lemma before anthesis. The TaSUT5 gene group was very weakly expressed in all tissues. The upregulated gene expression of TaSUT1 Westonia type in stem and grain reveal a crucial role in stem WSC remobilization to grain under drought. The high TaSUT1 gene expression and the significant correlations with thousand grain weight (TGW) and kernel number per spike demonstrated the contribution in Kauz's high grain yield in an irrigated environment and high TGW in Westonia under drought stress. Further molecular level identification is required for gene marker development.

Crystal structure of 5-[bis-(methyl-sulfon-yl)meth-yl]-1,3-dimethyl-5-(methyl-sulfon-yl)pyrimidine-2,4,6(1H,3H,5H)-trione.

In the title compound, C10H16N2O9S3, the pyrimidine ring of the 1,3-dimethyl barbituric acid moiety has an envelope conformation with the C atom carrying the methyl-sulfonyl and bis-(methyl-sulfon-yl)methyl substituents as the flap. The dihedral angle between mean plane of the pyrimidine ring and the S/C/S plane is 72.4 (3)°. In the crystal, mol-ecules are linked via C-H⋯O hydrogen bonds, forming a three-dimensional structure.

Mixed connective tissue disease: the King Faisal Specialist Hospital experience.

BACKGROUND: The aim of this study was to assess the clinical presentation, complications and serological analysis of mixed connective tissue disease (MCTD) at King Faisal Specialist Hospital & Research Centre (KFSH&RC), and to determine the long-term clinical and immunologic outcomes. PATIENTS AND METHODS: This was a retrospective study with prospective follow-up of 18 patients with MCTD who were followed at KFSH&RC between 1982 and 1999. RESULTS: The age at onset of the disease ranged from 6 to 44 years, with a mean age of 17.9 years. The female to male ratio was 2.5:1, and the mean follow-up time was 5 years. The most frequent presenting symptoms were arthralgia in all patients, Raynaud's phenomenon in 16 patients (88%) and swollen hands in 11 patients (61%). Arthritis was seen in 12 patients (67%) and definite myositis in 10 patients (58%). The most common skin rashes encountered included lupus-like rash in 8 patients (44%), scleroderma-like rash in 8 patients (44%), and cutaneous vasculitis in 5 patients (28%). Pulmonary hypertension occurred in 4 patients (22%). Other clinical manifestations encountered were esophageal hypomotility in 10 patients (56%), myocarditis in 2 patients (11%) and proteinuria in 2 patients (11%), while various neurological manifestations were present in 7 patients (39%). All patients exhibited high titer of ANA and anti-nRNP antibodies. Five of the 18 patients (28%) had marked reduction in the anti-nRNP during remission. Following treatment, features of inflammation as well as Raynaud's phenomenon and esophageal hypomotility diminished, while pulmonary hypertension persisted. A favorable outcome was observed in 12 patients (67%); 3 patients (17%) had continued active disease, while 3 patients (17%) died, with death related to pulmonary hypertension occurring in two patients (11%). CONCLUSION: The studied patients demonstrated the typical clinical and serological findings of MCTD, which support the correlation between anti-nRNP antibody specificities and MCTD. Autoantibody reactivity against nRNP polypeptides tends to regress during prolonged disease remission. The majority of our patients had favorable outcomes, with pulmonary hypertension being the most frequent disease-associated cause of morbidity and mortality.