Bis(benzofuran-thiazolidinone)s and bis(benzofuran-thiazinanone)s as inhibiting agents for chikungunya virus

Molecular basis of virus replication, viral pathogenesis and antiviral strategie

Quasistatic delamination of sandwich-like Kirchhoff-Love plates

A quasistatic rate-independent adhesive delamination problem of laminated plates with a finite thickness is considered. By letting the thickness of the plates go to zero, a rate-independent delamination model for a laminated Kirchhoff-Love plate is obtained as limit of these quasistatic processes. The same dimension reduction procedure is eventually applied to processes which are sensitive to delamination modes, namely opening vs. shearing is distinguishe

Os(CO)(2)(eta(2)-SC5H4N(O))(eta(2)-SC5H4N): structural evidence for the transformation of pyridine-2-thione N-oxide to pyridine-2-thiolate in osmium complexes

The reaction Of Os-3(CO)(12) with an excess of 1-hydroxypyridine-2-thione and Me3NO gives three mononuclear osmium complexes Os(CO)(2) (eta(2) -SC5H4N(O))(2) (1), Os(CO)(2)( eta(2)-SC5H4N(O))(eta(2)-SC5H4N) (2), and Os(CO)(2)(eta(2) -SC5H4N)(2) (3). The results of single-crystal X-ray analyses reveal that complex 1 contains two O,S-chelate pyridine-2-thione N-oxide (PyOS) ligands, whereas complex 2 contains one O,S-chelate PyOS and one N,S-chelate pyridine-2-thiolate group. The unique structure of 2 provides evidence of the pathway for this transformation. When this reaction was monitored by H-1 NMR spectroscopy the triosmium complexes Os-3(CO)(10)(mu-H)( mu-eta'-S-C5H4N(O)) (4) and Os-3(CO)(9)(mu-H)(mu-eta(1): eta2-SC5H4N(O)) (5) were identified as intermediates in the formation of the mononuclear final products 1-3. The proposed pathway is further supported by the observation of several dinu-clear osmium intermediates by electrospray ionization mass spectrometry. In addition, the reaction of Os-3(CO)(12) with 1-hydroxypyridine-2-thione in the absence of Me3NO at 90degreesC generated mononuclear complex 2 as the major product along with smaller amounts of complexes 1 and 3. These results suggest that the N-oxide facilitates the decarbonylation reaction. Crystal data for 1: monoclinic, space group C2/c, a = 26.9990(5) A, b = 7.6230(7) A, c = 14.2980(13) A, beta =101.620(2)degrees, V= 2882.4(4) A(3), Z = 8. Crystal data for 2: monoclinic, space group C2/c, a = 5.7884(3) angstrom, b = 13.9667(7) angstrom, c = 17.2575(9) A, beta = 96.686(l)degrees, V= 1385.69(12) angstrom (3), Z = 4. (C) 2004 Elsevier B.V. All rights reserved

Identification of radicals responsible for DNA cleavage by photolysis of bis-oxime esters

Newly synthesized 9, 10-anthraquinone and acenaphthene-1, 2-dione derivatives exhibited high potency for DNA scission under photolytic conditions at concentrations of 37 and 6.5 μM, respectively. Results from electron paramagnetic resonance (EPR) experiments reveal that the benzoyloxy radicals and their degraded aryl radical intermediates (rather than bis-iminyl radicals) were mostly responsible for the DNA cleavage

Identification of radicals responsible for DNA cleavage by photolysis of bis-oxime esters

Newly synthesized 9, 10-anthraquinone and acenaphthene-1, 2-dione derivatives exhibited high potency for DNA scission under photolytic conditions at concentrations of 37 and 6.5 μM, respectively. Results from electron paramagnetic resonance (EPR) experiments reveal that the benzoyloxy radicals and their degraded aryl radical intermediates (rather than bis-iminyl radicals) were mostly responsible for the DNA cleavage

Structural bases of norovirus RNA dependent RNA polymerase inhibition by novel suramin-related compounds

Noroviruses (NV) are +ssRNA viruses responsible for severe gastroenteritis; no effective vaccines/antivirals are currently available. We previously identified Suramin (9) as a potent inhibitor of NV-RNA dependent RNA polymerase (NV-RdRp). Despite significant in vitro activities versus several pharmacological targets, Suramin clinical use is hampered by pharmacokinetics/toxicity problems. To improve Suramin access to NV-RdRp in vivo, a Suramin-derivative, 8, devoid of two sulphonate groups, was synthesized, achieving significant anti-human-NV-RdRp activity (IC50 = 28 nM); the compound inhibits also murine NV (mNV) RdRp. The synthesis process led to the isolation/characterization of lower molecular weight intermediates (3-7) hosting only one sulphonate head. The crystal structures of both hNV/mNV-RdRps in complex with 6, were analyzed, providing new knowledge on the interactions that a small fragment can establish with NV-RdRps, and establishing a platform for structure-guided optimization of potency, selectivity and drugability

TeraHertz scattering : comparison of a novel theoretical approach with experiment

At the present time the interaction of Terahertz (THz) radiation with random structures is not well understood. Scattering effects are particularly relevant in this spectral regime, where the wavelength, and the size and separation of scattering centres are often commensurable. This phenomenon can both be used to advantage in imaging and sensing, but conversely can have adverse effects on the interpretation of a "fingerprint" spectrum. A new mathematical method, the Phase Distribution Model, is reported here for the calculation of attenuation and scattering of THz radiation in random materials. This uses a Phase Distribution Function to describe the effect of the non-absorbing scatterers within the media. Experimental measurements undertaken using previously published results, data obtained from specially constructed phantoms and from everyday textiles have been compared with the theory. These experimental results encompass both cylindrical and spherical scattering situations. The model has also been compared with exact calculations using the Pendry code