The reaction of 2,6-dimethyl-4-phenyl-1,4-dihydropyridine-3,5-dicarbohydrazide with variety of carbonyl compounds such as substituted benzaldehydes, cycloalkanones and hetero-cyclic ketones under grinding method under catalyst-and solvent-free conditions at room temperature, in the presence of catalytic drops of acetic acid gave a new series of 2,6-dimethyl-4-phenyl-1,4-dihydropyridine-3,5-dicarbohydrazone derivatives in good to excellent yields. The structures of new products were elucidated on the basis of their spectral data and elemental analysis. Most of the newly prepared compounds were evaluated towards HepG2 cell lines and showed good IC 50 for some compounds. Additionally, molecular docking of the novel chemical entities using Autodock Vina demonstrated their binding modes within the active site of DYRK1A.
L-asparaginase (EC 3.5.1.1), which catalyzes the deamidation of L-asparagine to L-aspartic acid and ammonia, has been widely used as a key therapeutic tool in the treatment of tumors. The current commercially available L-asparaginases, produced from bacteria, have signs of toxicity and hypersensitivity reactions during the course of tumor therapy. Therefore, searching for L-asparaginases with unique biochemical properties and fewer adverse effects was the objective of this work. In this study, cyanobacterial strain Synechococcus elongatus PCC6803 was found as a novel source of L-asparaginase. The L-asparaginase gene coding sequence (gi:939195038) was cloned and expressed in E. coli BL21(DE3), and the recombinant protein (Se.ASPII) was purified by affinity chromatography. The enzyme has high affinity towards L-asparagine and shows very weak affinity towards L-glutamine. The enzymatic properties of the recombinant enzyme were investigated, and the kinetic parameters (K, V) were measured. The pH and temperature dependence profiles of the novel enzyme were analyzed. The work was extended to measure the antitumor properties of the novel enzyme against different human tumor cell lines.
BackgroundPyridines have been reported to possess various pharmacological activities.ResultsSodium 3-oxo-3-(2-oxo-2H-chromen-3-yl)prop-1-en-1-olate (2) and sodium 3-oxo-3-(3-oxo-3H-benzo[f]chromen-2-yl)prop-1-en-1-olate (7) were prepared and reacted with 2-cyano-N’-(1-aryl(heteryl)ethylidene)acetohydrazides 3a–d to produce 2-oxo-1,2-dihydropyridine-3-carbonitrile derivatives 5a–d and 9a–d, respectively, in good yields. Also, 3a–d reacted with sodium (2-oxocyclopentylidene)methanolate (11a) or sodium (2-oxocyclohexylidene) methanolate (11b) to yield 2-oxo-tetrahydro-1H-cyclopenta[b]pyridine-3-carbonitriles 13a–d and 2-oxo-hexahydroquinoline-3-carbonitriles 13e–h, respectively. The mechanisms that account for the formation of the products are discussed. Additionally, the structures of all the newly synthesized products are confirmed, based on elemental analysis and spectral data. Several of the newly synthesized compounds are evaluated for their antitumor activity against HEPG2 and their structure activity relationship (SAR) was studied.ConclusionsThe results revealed that the pyridine derivatives 5c and 5d (IC50 = 1.46, 7.08 µM, respectively) have promising antitumor activity against liver carcinoma cell line (HEPG2), compared to the reference drug, doxorubicin.
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