Novel synthesis, ring transformation and anticancer activity of 1,3-thiazine, pyrimidine and triazolo[1,5-a]pyrimidine derivatives

Synthesis, heterocyclization and anticancer activity of a new series of heterocyclic compounds are described. Aminothiazine 1 was obtained from the base induced condensation of thiourea, benzaldehyde and ethyl cyanoacetate. The synthesis of N-phenyl amino pyrimidine derivative 2 was obtained as a result of reaction of aniline with compound 1. Compound 2 underwent ring opening and recyclization upon reaction with HCl or H2O2/ NaOH to afford the acid derivative 3 or oxazine 4, respectively. Thiazine 1 undergoes ring transformation upon the effect of NH2OH.HCl to produce pyrimidine derivative 5. Heterocyclization of compound 1 with thiosemicarbazide followed by oxidation with I2/AcOH afforded triazolopyrimidine 6 and 7, respectively. Alkylation of compound 1 was promoted by reaction of 1 with ethyl iodide to give alkylated thiazine 8 which in turn undergo ring transformation when subjected to reaction with hydrazine hydrate to give pyrazole derivative 9. Refluxing of amino-1,3-thiazine derivative 1 with ethyl bromoacetate in the presence of Et3N produce the alkylated pyrimidine product 10. Hydrazonolysis of 1,3-thiazine 1 with hydrazine or phenyhydrazine gave pyrimidine derivatives 11a,b, respectively. Compound 11b was cyclized with carbon disulfide or formaldehyde to produce triazolopyrimidines 12 and 13, respectively. Some of the new compounds were screened for anticancer activity and significant results were found for some compounds.               KEY WORDS: 1,3-Thiazine, Pyrimidine, Triazole, Pyrazole, Anticancer activity Bull. Chem. Soc. Ethiop. 2018, 32(3), 513-522.DOI: https://dx.doi.org/10.4314/bcse.v32i3.1

The mechanism of action of Spirulina as antidiabetic: a narrative review

Spirulina happens to be a special type of blue-green algae that originally emerged 3.5 billion years ago and was used as a source of nutrition. Spirulina gets its name from the filaments’ spiral or helical structure, but its true name is taxonomically Genus Arthrospira which encompasses several species. The most common species are S. fusiformis, S. maxima, and S. platensis. It is rich in various nutrients and chemical components including protein, carbohydrates, lipids, vitamins, minerals, pigments, chlorophyll, and enzymes. Spirulina’s active molecules and rich nutrients make it have several pharmacological activities and uses including antioxidant, anti-inflammatory, immunomodulatory, immune system booster, anticancer, antiviral activity, and neuroprotective properties. It is also utilized as a nutritional supplement and for weight loss. Moreover, several studies confirm that Spirulina improves insulin sensitivity and reduces blood glucose levels in rat models as well as diabetic patients. The reason behind this unique behavior could be credited to the presence of several active components in it, but the action’s fundamental mechanism is still a matter of debate. Several studies have suggested different mechanisms including anti-inflammatory activity, increased insulin sensitivity, inhibition of gluconeogenesis, antioxidant activity, modulating gut microbiota composition, improved glucose homeostasis, and insulin receptor activation. Therefore, it became clear that Spirulina is a mine of active substances used as a nutritional supplement and reduces blood glucose levels or used in conjunction with other treatments to tackle type 2 diabetes. Further exploration is required to fully explain its effects on human physiology and determine optimal dosages for treatment

MIR-99a and MIR-99b Modulate TGF-β Induced Epithelial to Mesenchymal Plasticity in Normal Murine Mammary Gland Cells

Epithelial to mesenchymal transition (EMT) is a key process during embryonic development and disease development and progression. During EMT, epithelial cells lose epithelial features and express mesenchymal cell markers, which correlate with increased cell migration and invasion. Transforming growth factor-β (TGF-β) is a multifunctional cytokine that induces EMT in multiple cell types. The TGF-β pathway is regulated by microRNAs (miRNAs), which are small non-coding RNAs regulating the translation of specific messenger RNAs

Polysiloxane-immobilized triamine ligand system, synthesis and applications

The polysiloxane-immobilized triamine ligand system of the formula P-(CH 2 ) 3 NH(CH 2 ) 2 NH(CH 2 ) 2 NH 2 (where P represents the siloxane network) has been prepared via the sol-gel process by hydrolytic polycondensation of (EtO) 4 Si and (MeO) 3 Si(CH 2 ) 3 NH(CH 2 ) 2 NH(CH 2 ) 2 NH 2 . An alternative method was used by the reaction of the iodopolysiloxane P-(CH 2 ) 3 -I and diethylenetriamine in the presence of triethylamine. The immobilized triamine ligand forms metal chelate complexes when treated with aqueous metal(II) ion solutions (Co 2+ , Ni 2+ , and Cu 2+ ). The elemental analysis and FTIR results suggest that this ligand system undergoes a substantial leaching of diethylenetriamine ligand moieties from the siloxane framework

Uptake of divalent metal ions (Cu2+, Ni2+, and Co2+) by polysiloxane immobilized triamine-thiol and thiol-acetate ligand system

Insoluble porous solid polysiloxanes-immobilized ligand systems bearing hybrid mixture of triamine-thiol ligand and thiol-acetate ligand as chelating functional groups of the general formula P-(CH2)3-X(Y) (Where P represents a silica like siloxane framework and X represents a mixture of triamine and thiol, -NHCH2)2NH-(CH2)2-NH2 and –SH, and Y represents a thiol-acetate -SCH2COOH functional groups) has been prepared. The immobilized triamine-thiol ligand system was prepared through the sol-gel process by hydrolytic polycondensation of Si(OEt)4 and a mixture of 3-mercaptopropyltrimethoxysilane and 3-diethylenetriaminepropyltrimethoxysilane coupling agents. The immobilized thiol-acetate ligand system was prepared by the reaction of polysiloxane immobilized thiol ligand with ethylchloroacetate. These ligand systems exhibit high potential for extraction and preconcentration of divalent metal ions (Co

Exogenously Applied Salicylic Acid Boosts Morpho-Physiological Traits, Yield, and Water Productivity of Lowland Rice under Normal and Deficit Irrigation

The main constraint on rice cultivation in the Mediterranean area is the limited irrigation and its large water consumption. In addition, rice is very sensitive to drought conditions because of drought stress on morpho-physiological traits and yield reduction. The application of salicylic acid (SA) has been noticed to be very effective in alleviating the adverse effects of drought stress on rice. The current investigation was conducted as a split-split arrangement under a randomized complete block design with two lowland rice cultivars (Giza177 and Giza179) and SA as a foliar application at four concentrations (0, 400, 700, and 1000 µM) under normal and drought conditions. The results showed that plant growth, leaf photosynthetic pigments, yields, and the most studied traits were significantly affected by irrigation (I), cultivar (C), and SA concentration (p ≤ 0.05 or 0.01). The interaction effect of I × C × SA was only significant on the carotenoids content (p ≤ 0.05). The reduction in grain yield and most studied traits was more pronounced under drought conditions. The Giza179 proved to be a drought-tolerant cultivar under all SA concentrations under drought conditions, while Giza177 was a drought-sensitive cultivar. The application of 700 µM SA gave the best grain yield in both rice cultivars under drought conditions compared to other SA concentrations. Grain yield for normal irrigation (Yp) and drought stress (Ys) conditions were highly positively correlated with indices of the mean productivity (MP), geometric mean productivity (GMP), stress tolerance index (STI), yield index (YI), yield stability index (YSI), drought resistance index (DI), harmonic mean (HM), and golden mean (GOL). While they are highly negatively correlated with the indices of the stress susceptibility index (SSI), tolerance index (TOL), yield reduction ratio (YR), stress susceptibility percentage index (SSPI), and abiotic tolerance index (ATI). It could be concluded that SA, as a growth regulator, could be used to alleviate the harmful effect of inadequate water availability in soil on rice cultivars as well as to improve the growth, water productivity, and grain yield