26 research outputs found
8a-Methyl-5,6,8,8a,9,10-hexahydro-10,12a-epoxyisoindolo[1,2-a]isoquinolinium iodide
The title compound, C17H18NO+·I−, is an adduct resulting from an intramolecular Diels–Alder reaction of methallyl chloride with 3,4-dihydro-1-furylisoquinoline. The cation comprises a fused pentacyclic system containing three five-membered rings (dihydropyrrole, dihydrofuran and tetrahydrofuran) and two six-membered rings (tetrahydropyridine and benzene). The five-membered rings have the usual envelope conformations, and the central six-membered tetrahydropyridine ring adopts the unsymmetrical half-boat conformation. In the crystal, cations and iodide anions are bound by weak intermolecular hydrogen-bonding interactions into a three-dimensional framework
(6aS*,6bS*,11R*,11aR*)-6-(2-Furylmethyl)-5,12-dioxo-5,6,6a,6b,7,11,11a,12-octahydrofuro[3′,2′:5,6]isoindolo[2,1-a]quinazoline-11-carboxylic acid
The title compound, C23H18N2O6, is the product of an intramolecular thermal cycloaddition within 1-malein-2-[(E)-2-(2-furyl)vinyl]-4-oxo-3,4-dihydroquinazoline. The molecule comprises a previously unknown fused pentacyclic system containing two five-membered rings (2-pyrrolidinone and furan) and three six-membered rings (benzene, 2,3-dihydro-4-pyrimidinone and dihydrocyclohexane). The central five-membered pyrrolidinone ring has the usual envelope conformation. The six-membered dihydropyrimidinone and dihydrocyclohexane rings adopt a half-boat and a half-chair conformation, respectively. The dihedral angle between the planes of the terminal benzene and furan rings is 45.99 (7)°. In the crystal, O—H⋯O hydrogen bonds link the molecules into centrosymmetric dimers. Weak C—H⋯O hydrogen bonds consolidate further the crystal packing, which exhibits π–π interactions, with a short distance of 3.556 (3) Å between the centroids of benzene rings of neighbouring molecules
Apoptosis induction in human leukemia cells by novel 2-amino-5-benzylthiazole derivatives
Derivatives of 2-amino-5-benzylthiazole are heterocyclic pharmacophores that exhibit different pharmacological activities including anticancer action. The mechanisms of such action of these compounds are not clear. The aim of the present study was to investigate apoptosis induction, particularly DNA damage in human leukemia cells, by the novel synthesized thiazole derivatives ‒ 2,8-dimethyl-7-(3-trifluoromethyl-benzyl)pyrazolo[4,3-e]thiazolo[3,2-a]pyrimidin-4(2H)-one (compound 1) and 7-benzyl-8-methyl-2-propylpyrazolo[4,3-e]thiazolo[3,2-a]pyrimidin-4(2H)-one (compound 2). Western-blot analysis, DNA comet assay in alkaline conditions, diphenylamine DNA fragmentation assay, agarose gel retardation, and methyl green DNA intercalation assays were used to study the effects of the studied compounds in human leukemia cells. These compounds induced PARP1 and caspase 3 cleavage in the leukemia cells, also increased the level of pro-apoptotic Bim protein and the mitochondrion-specific EndoG nuclease, and decreased the level of the anti-apoptotic Bcl-2 protein. They caused DNA single-strand breaks and DNA fragmentation in the leukemia cells without direct DNA binding or DNA intercalation. Thus, novel 2-amino-5-benzylthiazole derivatives may be promising agents for apoptosis induction in the targeted human leukemia cells
SYNTHESIS OF HETEROCYCLES ON THE BASIS OF ARYLATION PRODUCTS OF UNSATURATED COMPOUNDS. 11. 1
2‐Bromo‐2‐chloro‐3‐arylpropanenitriles as C‐3 synthons for the synthesis of functionalized 3‐aminothiophenes
2-Bromo-2-chloro-3-arylpropanenitriles can be prepared by Meerwein reaction from 2-chloroacrylonitrile and various aryldiazonium salts under copper(II) bromide catalysis. They proved to be stable compounds which form 2-chlorocinnnamonitriles upon treatment with bases. Reaction of the title compounds with substituted thioglycolates gave substituted 3-aminothiophenes which have not yet been accessible by other routes. Three-component reactions with the title compound, sodium sulfide and bromonitromethane, chloroacetonitrile, or ethyl 4-chloroacetoacetate gave 2-nitro- and 2-cyano-substituted 3-aminothiophenes, and thienopyridinediones in high yields and in one single step, respectively
Utilization of Methyl 3-Aryl-2-thiocyanatopropanoates in the Synthesis of 2-(4-Morpholinyl)- and 2-(Piperazinyl)-5-(benzyl)thiazol-4-ones 1
2‐Bromo‐2‐chloro‐3‐arylpropanenitriles as C‐3 Synthons for the Synthesis of Functionalized 3‐Aminothiophenes
Effects of new derivatives of 2-amino-5-benzylthiazole of genotoxicity and acute toxicity in Allium bioassays
We have found that new derivatives of 2-amino-5-benzylthiazole possess cytotoxic action towards human tumor cells (Finiuk et al., Biopolym. Cell, 2017; Finiuk et al., Ukr. Biochem. J., 2018). A release of the chemotherapeutic drugs into the environment may cause adverse effects towards ecosystems. To promote further these derivatives as potential anticancer agents, it was necessary to evaluate their genotoxicity and acute toxicity, namely in plants that have an important trophic level in ecosystems. To do that, we used towards plant bioassays for new derivatives of N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide (compound 1) and 2,8-dimethyl-7-(3-trifluoromethyl-benzyl)pyrazolo[4,3-e]thiazolo[3,2-a]pyrimidin-4-one (compound 2). Allium cepa ana-telophase assay was applied to monitor the genotoxicity of the studied compounds. Besides, the acute toxic effects such as inhibition of cell division, seed germination and growth of Allium roots were estimated. The compound 1 (10 mM) in concentration equal to the IC50 for tumor cells, and compound 2 in 1 mM (1´ concentration, equal to the IC50 for tumor cells) and 10 mM (10´ concentration) did not possess acute toxicity towards Allium cepa. A significant inhibition of root growth and seed germination effects were detected at using the compound 1 only in dose that is 10 times higher than the IC50 for tumor cells. The ana-telophase assay did not reveal the genotoxic effect of the compounds 1 (10 mM) and 2 (1 and 10 mM). The compounds 1 (10 mM) and 2 (1 and 10 mM) did not affect the mitotic and phase (prophase, metaphase, anaphase, telophase) indices. A commercial anticancer drug Doxorubicin (0.1 and 1 mM) possessed a significant inhibitory effect on root growth and seed germination, mitotic index and enhanced a level of chromosomal aberrations in Allium cepa. The compound 1 at 10 mM and compound 2 at 1 mM and 10 mM did not possess a significant acute toxicity (inhibition of cell division, seed germination and growth of Allium roots), did not demonstrated the genotoxic effects (induction of chromosomal aberrations) in Allium bioassay. These results give primary evidence about a possibility of using the synthetic 2-amino-5-benzylthiazole derivatives – compounds 1 and 2 – as novel antineoplastic agents that will have no negative side effects in the treated plant organism. Additional experiments should be performed in order to evaluate the adverse effects of new derivatives of 2-amino-5-benzylthiazole in a vide spectrum of the concentrations for the prediction of environmental toxicity and genotoxicity of chemicals
Novel Selected Tandem Transformations of the Amino and Carbonyl/Nitrile Groups in the Gewald Thiophenes
Evaluation of antiproliferative activity of pyrazolothiazolopyrimidine derivatives
The research aim was to test cytotoxic effects in vitro of seven novel pyrazolothiazolopyrimidine derivatives in targeting several lines of tumor and pseudo-normal mammalian cells. We demonstrated that cytotoxic effects of these derivatives depended on the tissue origin of targeted cells. Leukemia cells were found to be the most sensitive to the action of compounds 2 and 7. Compound 2 demonstrated approximately two times higher toxicity towards the multidrug-resistant sub-line of HL-60/ADR cells compared to the Doxorubicin effect. Antiproliferative action of compounds 2 and 7 dropped in the order: leukemia > melanoma > hepatocarcinoma > glioblastoma > colon carcinoma > breast and ovarian carcinoma cells. These compounds were less toxic than Doxorubicin towards the non-tumor cells. The novel pyrazolothiazolopyrimidine, compound 2, demonstrated high toxicity towards human leukemia and, of special importance, towards multidrug-resistant leukemia cells, and low toxicity towards pseudo-normal cells