We used complexes between a fourth generation polyamidoamine (PAMAM) dendrimer and one of two heterocyclic compounds — 1-(6-hydroxyhexyl)-3-(5-phenyl-isoxazole-3-yl)-urea or ...5-phenyl-isoxazole-3-carboxylic acid — to reduce oxygen consumption in transverse slices of the hippocampus taken from 4-week old male rats. In vitro electrophysiological experiments revealed that the inhibitory effect of the hypoxic state on the evoked responses was enhanced in the presence of the complexes. The data were analyzed in terms of the potential antitumor effects of these complexes.
N-Furfuryl allylamines, readily accessible from corresponding furfurals or furfuryl amines, react with a broad range of arylsulfonyl chlorides with the formation of a 3a,6-epoxyisoindole core in one ...synthetic stage. Usually, in boiling water, the interaction sequence involves two consecutive steps: the Hinsberg reaction and the intramolecular Diels–Alder furanе (IMDAF) reaction. The scope and limitations of the proposed method were thoroughly investigated, and it was revealed that the key 4 + 2 cycloaddition step proceeds through an exo-transition state, giving rise to the exclusive formation of a single diastereomer of the target heterocycle. The method allows the ability to obtain N-sulfaryl-substituted 3a,6-epoxyisoindoles and 4a,7-epoxyisoquinolines, which are potentially useful substrates for further transformations and subsequent bioscreening, in particular antimicrobial activity.
Display omitted
•A short IMDAF strategy to give 2-(arylsulfonyl)-3a,6-epoxyisoindoles from readily available initial materials was proposed.•Cascade of the Hinsberg / IMDAF Reactions is very simple and strongly depends on the characteristics of substituents.•Aforesaid epoxyisoindoles possess antibacterial activity against gram-negative or gram-positive sensitive bacteria strains.
A series of N-acyl derivatives of anabasine and cytisine were prepared, to discover novel, natural product-based medicinal agents. All synthesized compounds were tested for antimicrobial, antifungal, ...antiviral and analgesic activity. The most pronounced antibacterial activity was shown by the compounds with isoxazole fragments, while the adamantane derivatives showed the greatest antiviral effect. It was found that the majority of anabasine derivatives showed significant analgesic activity, reducing the pain response of animals to the irritating effect of acetic acid. The presence of a high level of antimicrobial and antiviral activity in newly synthesized compounds makes it possible to consider them promising for further study of their pharmacological properties.
New substituted 3-((1H-1,2,3-triazol-1-yl)methyl)-5-arylisoxazoles (aryl = Ph, p-Tol) and ...2-(5-phenylisoxazol-3-yl)-5-(2-(1-((5-(p-tolyl)isoxazol-3-yl)methyl)-1H-1,2,3-triazol-4-yl)ethyl)-1,3,4-oxadiazole were synthesized by means of click-chemistry procedures. The obtained compounds were used as ligands in preparation of palladium(II) complexes, and the latter proved to be high-turnover-number catalysts for CC cross-coupling reactions under Green Chemistry conditions. One of the ligands was structurally characterized by single crystal X-ray diffraction, and the structure of complexes was determined by 1H, 13C, 15N NMR spectroscopy and quantum-chemical modeling.
Display omitted
In the title compound, C
21
H
22
N
2
O
3
S, the 1,2-oxazole ring makes the dihedral angles of 9.16 (16) and 87.91 (17)°, respectively, with the toluene and phenyl rings, while they form a dihedral ...angle of 84.42 (15)° with each other. The C—S—N—C
pr
and C—S—N—C
me
(pr = propene, me = 3-methyl-1,2-oxazole) torsion angles are 86.8 (2) and −100.6 (3) °, respectively. In the crystal, molecules are linked by C—H...O hydrogen bonds, generating a three-dimensional network. A Hirshfeld surface analysis was performed to investigate the contributions of the different intermolecular contacts within the supramolecular structure. The major interactions are H...H (53.6%), C...H/H...C (20.8%) and O...H/H...O (17.7%).
Oligopyridine based copper(II) complexes are of interest to scientists as possible anticancer agents due to promising cytotoxic and DNA binding/cleaving properties. In this study, copper(II) complex ...Cu(phendione)L
2
·C
2
H
5
OH with 1,10-phenanthroline-5,6-dione (phendione) and 4,5-dichloro-isothiazole-3-carboxylic acid (HL) was synthesized and characterized by elemental analysis, IR-spectroscopy, X-ray powder diffraction and single-crystal X-ray diffraction. According to X-ray diffraction data, obtained compound is mononuclear complex with square pyramidal coordination environment of the central atom which is surrounded by two isothiazolate molecules and one phendione ligand. The X-ray diffraction data are confirmed by IR-spectroscopy data showing the presence of characteristic stretching vibration bands of the carbonyl and carboxyl groups of oligopyridine ligand and isothiazolate ions, respectively. Density functional theory (DFT) calculations for complex were carried out using the ADF software package to perform geometry optimization and frequency calculations that were in a good agreement with experimental IR spectrum. Cytotoxicity of complex and initial reagents was tested in vitro against HepG2 (human hepatocellular carcinoma) and MCF-7 (human breast adenocarcinoma) cell lines. The complex showed high dose-dependent cytotoxic activity with the IC
50
values of 0.60±0.03 µM and 0.96±0.13 µM, respectively, which is higher than the activity of cisplatin against these cell lines. The activity of the complex is due to the presence of phendione ligand, which exhibits a similar cytotoxic activity.
It was found that the reaction of 5-arylfurfurilamines with maleic anhydride leads to the formation of 6-aryl-3a,6-epoxyisoindole-7-carboxylic acids (the cyclic form), which in solution are in ...dynamic equilibrium with N-furfurylmaleinamides (the open form). During the esterification of these tautomeric mixtures with methanol in the presence of a catalytic amount of sulfuric acid, methyl esters of 5-aryl-7a-hydroxy-7-methoxy-3-oxo-2,3,3a,4,7,7a-hexahydro-1H-isoindole-4-carboxylic acids, unexpected cleavage products of the 3a,6-oxo bridge of the cyclic form, are formed diastereospecifically. The structure of the obtained products was confirmed by X-ray structural analysis.
Methyl 5-hydroxy-4-oxo-4H-pyran-2-carboxylate was synthesized by esterification of methanol with comenic acid under acidic catalysis. The obtained ester was alkylated with ...3-(chloromethyl)-5-phenylisoxazole and 4,5-dichloro-3-(chloromethyl)isothiazole to afford corresponding conjugates containing isoxazole and isothiazole moieties which then were transformed into water-soluble Li-salts. During the bioassays of synthesized isoxazole and isothiazole derivatives of comenic acid in mixtures with first-line antitumor drug Temobel (Temozolomid) used in brain tumors chemotherapy, a synergetic effect was observed.
Halogenation of 9-dimethylsulfonium-7,8-dicarba-
nido-undecaborane 9-SMe
2-7,8-C
2B
9H
11 gave halogen derivatives 9-SMe
2-11-X-7,8-C
2B
9H
10, where X
=
Cl, Br, I. In the bromination reaction, 9-SMe
...2-6-Br-7,8-C
2B
9H
10 was isolated as a minor product being the first example of substitution at a “lower” belt of the 7,8-dicarba-
nido-undecaborate cage. The use of excess of bromine resulted in dibromo derivative 9-SMe
2-6,11-Br
2-7,8-C
2B
9H
9.
Halogenation of 9-dimethylsulfonium-7,8-dicarba-
nido-undecaborane 9-SMe
2-7,8-C
2B
9H
11 with
N-chlorosuccinimide, bromine and iodine gave the expected corresponding halogen derivatives 9-SMe
2-11-X-7,8-C
2B
9H
10, where X
=
Cl (
1), Br (
2), I (
3). In the bromination reaction, 9-SMe
2-6-Br-7,8-C
2B
9H
10 (
4) was isolated as a minor product being the first example of substitution at a “lower” belt of the 7,8-dicarba-
nido-undecaborate cage. The use of excess of bromine resulted in dibromo derivative 9-SMe
2-6,11-Br
2-7,8-C
2B
9H
9 (
5). Structures of the compounds prepared were determined using
11B–
11B COSY NMR spectroscopy (for all halogen derivatives) and single crystal X-ray diffraction (for compounds
2,
3, and
5).
Display omitted
•The adsorption of ciclopirox on the B12N12 and Se- B12N12 nanoclusters was studied.•Decoration of selenium on the B12N12 nanocluster reduces the band gap.•Se- B12N12 nanocluster is a ...promising drug delivery system.
Despite the significant role of ciclopirox as a novel anticancer agent to treat various cancers such as breast, liver, colorectal and bladder, it has some adverse effects and poor solubility in water. Hence, the enhancement of ciclopirox polarity is crucial in biological systems. In this work, the effect of selenium decoration on the interaction of ciclopirox drug molecule with B12N12 was investigated using density functional theory (DFT) calculations. Based on structural analysis, CO group of ciclopirox was chemisorbed on the boron and selenium atoms of B12N12 and Se-B12N12 nanoclusters, respectively. It was found that the selenium decoration significantly improves the reactivity of B12N12 toward ciclopirox. A short recovery time (~2.13 s) was predicted for ciclopirox desorption from the Se-B12N12 nanocluster surface. The vibrational frequency analysis was conducted to survey the vibration frequencies of bonds formed in the CPX/nanocluster complex. The charge transfer process was studied using charge decomposition analysis (CDA). Furthermore, Quantum theory of atoms in molecules (QTAIM) analysis revealed that the non-covalent interactions between CPX and nanoclusters are essential for the delivery process. Finally, electronic properties analysis showed that energy band gap of Se-B12N12 nanocluster is significantly reduced from 0.2835 to 0.2121 a.u after ciclopirox adsorption.
PDF
