Inhibition of Hsp90 with synthetic macrolactones: synthesis and structural and biological evaluation of ring and conformational analogs of radicicol

A series of benzo-macrolactones of varying ring size and conformation has been prepared by chemical synthesis and evaluated by structural and biological techniques. Thus, 12- to 16-membered lactones were obtained by concise routes, involving ring-closing metathesis as a key step. In enzyme assays, the 13-, 15-, and 16-membered analogs are good inhibitors, suggesting that they can adopt the required conformation to fit in the ATP-binding site. This was confirmed by cocrystallization of 13-, 14-, and 15-membered lactones with the N-terminal domain of yeast Hsp90, showing that they bind similarly to the "natural" 14-membered radicicol. The most active compounds in the ATPase assays also showed the greatest growth-inhibitory potency in HCT116 human colon cancer cells and the established molecular signature of Hsp90 inhibition, i.e., depletion of client proteins with upregulation of Hsp70.     

NIP for some pair-like theories

Generalising work of Berenstein, Dolich and Onshuus (Preprint 145 on MODNET Preprint server, 2008) and Günayd?n and Hieronymi (Preprint 146 on MODNET Preprint server, 2010), we give sufficient conditions for a theory T _P to inherit N I P from T, where T _P is an expansion of the theory T by a unary predicate P. We apply our result to theories, studied by Belegradek and Zilber (J. Lond. Math. Soc. 78:563?C579, 2008), of the real field with a subgroup of the unit circle.     

Synthetic ansamycins prepared by a ring-expanding Claisen rearrangement. Synthesis and biological evaluation of ring and conformational analogues of the Hsp90 molecular chaperone inhibitor geldanamycin

A series of ansa-quinones has been prepared by chemical synthesis, and evaluated by biological techniques. Thus, 19-membered ansa-lactams, simplified analogues of the naturally occurring Hsp90 molecular chaperone inhibitor geldanamycin, were obtained by concise routes, the key steps being the combination of a ring-closing metathesis to give a 17-membered ring followed by Claisen rearrangement to effect ring expansion. The methodology was also used to prepare an "unnatural" 18-membered ring analogue. In ATPase enzyme assays, the synthetic ansa-quinones were weak inhibitors of Hsp90.     

Solitary wave solutions to nonlinear evolution equations in mathematical physics

This paper obtains solitons as well as other solutions to a few nonlinear evolution equations that appear in various areas of mathematical physics. The two analytical integrators that are applied to extract solutions are tan–cot method and functional variable approaches. The soliton solutions can be used in the further study of shallow water waves in (1+1) as well as (2+1) dimensions.     

Heterogeneous photocatalyzed degradation of a pesticide derivative, 3-chloro-4-methoxyaniline, in aqueous suspensions of titania

The photocatalyzed degradation of a pesticide derivative, 3-chloro-4-methoxyaniline (1), has been investigated in aqueous suspensions of titanium dioxide (TiO₂) and air as a function of irradiation time under a variety of conditions using UV?CVis spectroscopic and HPLC analysis techniques. The degradation kinetics were studied under different conditions such as types of TiO₂ powders, reaction pH, catalyst loading, substrate, and H₂O₂ concentrations. The photocatalyst Degussa P25 showed better photocatalytic activity for the degradation of the compound 1. Addition of hydrogen peroxide as an electron acceptor in addition to oxygen greatly enhanced the degradation rate of the compound 1. Higher degradation rates were observed at lower and higher pH values, i.e., 3.15 and 9.15, respectively. The optimal substrate concentration and catalyst loading for the degradation was found to be 0.6?mM with 1.5?g?L^?1. A probable pathway for the decomposition of compound 1 is proposed.