1H, 13C and 15N NMR data for indolo[2,3-b]quinolines, a novel potent anticancer drug family.

The complete NMR signal assignment of title compounds were carried out by extensive use of 1D and 2D NMR techniques (1H, 13C, COSY, HSQC and HMBC).

Binding of topotecan to a nicked DNA oligomer in solution.

Topotecan (TPT) is in clinical use as an antitumor agent. It acts by binding to the covalent complex formed between nicked DNA and topoisomerase I, and inserts itself into the single-strand nick, thereby inhibiting the religation of the nick and acting as a poison. A crystal structure analysis of the ternary complex has shown how the drug binds (B. L. Staker, K. Hjerrild, M. D. Feese, C. A. Behnke, A. B. Burgin, L. Stewart, Proc. Natl. Acad. Sci. U.S.A., 2002, 99, 15 387-15 392), but has left a number of unanswered questions. Herein, we use NMR spectroscopy and molecular modeling to show that the solution structure of a complex of TPT with nicked natural DNA is similar, but not identical to the crystal conformation, and that other geometries are of very low population. We also show that the lactone form of TPT binds approximately 40 times more strongly than the ring-opened carboxylate.

1H and 13C NMR data for indolo[2,3-b]quinoline-aminoglycoside hybrids, a novel potent anticancer drug family.

The complete NMR signal assignment of title compounds were carried out by extensive use of 1D and 2D NMR techniques (1H, 13C, GCOSY, GHSQC and GHMBC).

Effects of ethanol on flash-evoked potentials of rats: lack of antagonism by naltrexone.

The present study examined the effects of ethanol and naltrexone hydrochloride (a nonselective opiate receptor antagonist) on flash-evoked potentials recorded from both the visual cortex (VC) and the superior colliculus (SC) of chronically implanted hooded rats. There were four treatment conditions administered on separate days: Either saline or naltrexone (10 mg/kg; volume of 1.0 ml/kg) was given 10 min before either saline or ethanol (2.0 g/kg; 20% ethanol solution in a volume of 1.26 ml/100 g). Evoked potentials were recorded 15 min after the intraperitoneal injections were completed. Animals were tested at 23.1 degrees C room temperature. In the VC, ethanol significantly decreased the amplitude of components N1, P3, and N3, whereas it increased the amplitude of P2. Components P1 and N2 were unaffected by ethanol treatment. The SC components P3 and N4 were reduced in amplitude by ethanol, but component P1 was not altered. Latencies of all components in both structures were increased by ethanol. Naltrexone alone did not significantly affect the potentials, nor did naltrexone pretreatment significantly alter the effects of ethanol on the potentials. Naltrexone produced a modest hypothermia of about 0.25 degrees C, whereas ethanol resulted in hypothermia of about 1.0 degrees C. Ethanol, either alone or in combination with naltrexone, significantly reduced body movement during the evoked-potential recording sessions. The results indicate that endogenous opioid systems do not play a major role in the acute effects of ethanol on flash-evoked potentials recorded from primary areas of the visual system.

NMR studies on three optical active drug molecules.

NMR spectroscopy is one of very few methods that enable deep insight into molecular structure and distinguishing of enantiomers. It usually requires the use of optically active agents that differentiate S and R forms through an interaction with studied molecule differentiate S and R forms. The aim of the present studies was to perform a preliminary NMR study on three chiral drugs: Fluoxetine hydrochloride, Ibuprofen, and Zolmitriptan by use of three optical solvating agents: R(-) 2,2,2-trifluoro-1-(9-anthryl)ethanol (I), (R)(+) 1,1'-bi-2-naphthol (II), and (S) tert-butyl-phenylphosphinothioic acid (III).

A nicked duplex decamer DNA with a PEG(6) tether.

A dumbbell double-stranded DNA decamer tethered with a hexaethylene glycol linker moiety (DDSDPEG), with a nick in the centre of one strand, has been synthesised. The standard NMR methods, E.COSY, TOCSY, NOESY and HMQC, were used to measure (1)H, (31)P and T:(1) spectral parameters. Molecular modelling using rMD-simulated annealing was used to compute the structure. Scalar couplings and dipolar contacts show that the molecule adopts a right-handed B-DNA helix in 38 mM phosphate buffer at pH 7. Its high melting temperature confirms the good base stacking and stability of the duplex. This is partly attributed to the presence of the PEG(6) linker at both ends of the duplex that restricts the dynamics of the stem pentamers and thus stabilises the oligonucleotide. The inspection of the global parameters shows that the linker does not distort the B-DNA geometry. The computed structure suggests that the presence of the nick is not disturbing the overall tertiary structure, base pair geometry or duplex base pairing to a substantial extent. The nick has, however, a noticeable impact on the local geometry at the nick site, indicated clearly by NMR analysis and reflected in the conformational parameters of the computed structure. The (1)H spectra also show much sharper resonances in the presence of K(+) indicating that conformational heterogeneity of DDSDPEG is reduced in the presence of potassium as compared to sodium or caesium ions. At the same time the (1)H resonances have longer T:(1) times. This parameter is suggested as a sensitive gauge of stabilisation.

[Ultrasonic diagnosis of tendon and ligament injuries in anterior dislocations of the shoulder joint]. / Ultrasonografia w rozpoznawaniu urazowych uszkodzen sciegnowo-wiezadlowych w przednich zwichnieciach stawu ramiennego.

The usefulness of ultrasonography in diagnosis of frequently occurring traumatic injuries of the ligament-tendon apparatus of the shoulder has been evaluated and compared with intra-operative nd contrast roentgenography examinations. An analysis of 102 cases, including 85 fresh anterior dislocation, 17 habitual anterior dislocation, has been made. 306 ultrasonographic examinations have been performed. A frequent coexistence of injuries of the tendon of the long head of the biceps muscle with an injury of the rotators cuff, mainly the supraspinous muscle, has been pointed out. The purposefulness of routine ultrasonographic examinations in injuries of the shoulder, especially acute, and full consideration of indications of early surgical treatment have been stressed.