Hydroxamic acid derivatives as histone deacetylase inhibitors: a DFT study of their tautomerism and metal affinities/selectivities.

Hydroxamic acids are regarded as potent inhibitors of histone deacetylases (HDAC), and can therefore be used to reduce malignancy growth and size in affected organisms. Although there is a substantial body of information on the structures, syntheses, and biological activities of HDAC inhibitors, several important questions regarding their physicochemical properties and metal affinities/selectivities remain answered. First, how do the conformation and ionization of the hydroxamic group depend on its chemical composition and the dielectric properties of the medium? Second, how do these factors affect the affinities and selectivities of HDAC inhibitors for essential biogenic metal cations? Third, what is the preferred deprotonation site of the hydroxamic moiety and its mode of binding to the metal cation? The present work addressed these questions by performing density functional calculations combined with polarizable continuum model computations.

Combretastatin A-4 analogues with benzoxazolone scaffold: Synthesis, structure and biological activity.

In order to design and synthesize a new class of heterocyclic analogues of natural combretastatin A-4 and its synthetic derivative AVE8062, the benzoxazolone ring was selected as a scaffold for a bioisosteric replacement of the ring B of both molecules. A library of 28 cis- and trans-styrylbenzoxazolones was obtained by a modified Wittig reaction under Boden's conditions. Structures of the newly synthesized compounds bearing the 3,4,5-trimethoxy-, 3,4-dimethoxy-, 3,5-dimethoxy-, and 4-methoxystyryl fragment at position 4, 5, 6 or 7 of benzoxazolone core were determined on the basis of spectral and X ray data.

[Characteristics of sexual maturation in girls in Bratislava region].

Objective: Evaluation of puberty onset and menarche in girls in Bratislava region in the years 2006-2007 and 2011-2013.

Design: Regional retrospective epidemiological study.

Setting: 1st Department of Gynaecology and Obstetrics, School of Medicine, Comenius University and University Hospital Bratislava, Slovenské republika.

Endolysin of bacteriophage BFK20: evidence of a catalytic and a cell wall binding domain.

A gene product of ORF24' was identified on the genome of corynephage BFK20 as a putative phage endolysin. The protein of endolysin BFK20 (gp24') has a modular structure consisting of an N-terminal amidase_2 domain (gp24CD) and a C-terminal cell wall binding domain (gp24BD). The C-terminal domain is unrelated to any of the known cell wall binding domains of phage endolysins.

Isolation and characterization of bacteriophage PhiBP from Paenibacillus polymyxa CCM 7400.

A bacteriophage PhiBP infecting Paenibacillus polymyxa CCM 7400 was isolated from culture lysate. Electron microscopy of lysate samples revealed the presence of bacteriophage particles with polyhedral heads 56 nm in diameter and flexible noncontractile tails 144 nm in length. The profile of PhiBP structural proteins resembles that of other bacteriophages.