Novel boronated derivatives of 5,10,15,20-tetraphenylporphyrin: synthesis and toxicity for drug-resistant tumor cells

We have developed the synthesis of boronated porphyrins for potential application in cancer treatment, based on the functional derivatives of 5,10,15,20-tetraphenylporphyrin. Boronated amide derivatives starting from 5,10,15,20-tetra(p-aminophenyl)porphyrin and 9-o- and 9-m-carborane carboxylic acid chlorides were prepared. Also, the reaction of 2-formyl-5,10,15,20-tetraphenylporphyrin with closo-C-lithium-o- and m-carboranes, as well as with closo-C-lithium monocarbon carborane, yielded neutral and anionic boronated hydroxy derivatives of 5,10,15,20-tetraphenylporphyrin, respectively. Water-soluble forms of neutral compounds were prepared by deboronation of closo-polyhedra with Bu4NF into nido-7,8- and nido-7,9-dicarbaundecaborate anions. Monocarbon carborane conjugated with copper (II) complex of 5,10,15,20-tetraphenylporphyrin was active for a variety of tumor cell lines (IC50 approximately 5 microM after 48-72 h of exposure) but was inert for non-malignant fibroblasts at up to 100 microM. At low micromolar concentrations, this compound caused the death of cells that express P-glycoprotein and other mechanisms of resistance to conventional anticancer drugs.     

Botulinum neurotoxin inhibitor binding dynamics and kinetics relevant for drug design

BackgroundA natural product analog, 3-(4-nitrophenyl)-7H-furo[3,2-g]chromen-7-one, which is a nitrophenyl psoralen (NPP) was found to be an effective inhibitor of botulinum neurotoxin type A (BoNT/A).MethodsIn this work, we performed enzyme inhibition kinetics and employed biochemical techniques such as isothermal calorimetry (ITC) and fluorescence spectroscopy as well as molecular modeling to examine the kinetics and binding mechanism of NPP inhibitor with BoNT/A LC.ResultsStudies of inhibition mechanism and binding dynamics of NPP to BoNT/A light chain (BoNT/A LC) showed that NPP is a mixed type inhibitor for the zinc endopeptidase activity, implying that at least part of the inhibitor-enzyme binding site may be different from the substrate-enzyme binding site. By using biochemical techniques, we demonstrated NPP forms a stable complex with BoNT/A LC. These observations were confirmed by Molecular Dynamics (MD) simulation, which demonstrates that NPP binds to the site near the active site.ConclusionThe NPP binding interferes with BoNT/A LC binding to the SNAP-25, hence, inhibits its cleavage. Based on these results, we propose a modified strategy for designing a molecule to enhance the efficiency of the inhibition against the neurotoxic effect of BoNT.General significanceInsights into the interactions of NPP with BoNT/A LC using biochemical and computational approaches will aid in the future development of effective countermeasures and better pharmacological strategies against botulism.     

Zooplankton in the Vychegda River

The species composition of plankton invertebrates was studied in the middle Vychegda River (the main tributary of the Northern Dvina River) in 2003–2005. A list of planktonic rotifers and lower crustaceans was made. The dominating complexes of zooplankton organisms were found. The quantitative characteristics of plankton communities in the river were described.     

Some Notes on the Morphology of an Aberrant Actinian (Hexacorallia, Actiniaria) Associated with the Glaucothoe of the Hermit Crab Paguropsis typica Henderson (Anomura, Paguridae)

The planktonic glaucothoe of the Indo-West Pacific hermit crab Paguropsis typica Henderson has an aberrant anthozoan polyp, identified as a nynanthean actinian, attached to the underside of its thorax. The morphology of the anemone is described. The scapus is dumb-bell shaped and exhibits a slit-like mouth opening oriented transverse to the animal's siphonoglyphal plane. The gonads are very well developed, whereas tentacle-like structures or retractor muscles of certain septa are reduced. In the adult stage, Paguropsis typica is associated with the zoanthidean Epizoanthus paguropsides . It is assumed that the actinian is lost at the ecdysis leading to the first "hermit stage" and that P. typica might possibly seize a free Epizoanthus colony and adapt it to its body.     

Structural changes in the rat myocardium in the process of adaptation to high-altitude hypoxia]

Changes in the weight of diverse parts of the heart, in cross-sectional area of myocytes and vascularization of the myocardium were studied in rat experiments under altitude hypoxia (3200 m above the sea level) during adaptation of the animals to hypoxia. Morphologically, the compensatory and adaptive reactions of the rat to hypoxia were shown by its increases weight at the expense of hypertrophy of the right ventricular myocardium. Vascularization of the myocardium augmented synchronously to its growing hypertrophy.     

Genetic diversity of tick-borne pathogenes in Tomsk and environs

Two urban and two suburban biotopes of Tomsk were studied for tick-transmitted disease prevalence in ticks collected in the wild. Tick-borne encephalitis virus (TBEV), West Nile virus (WNV), Borrelia spp., Rickettsia spp., and Ehrlichia spp. were found in 6.5%, 2.2%, 8%, 2.5%, and 1.7% of tick specimens, respectively. Genetic markers of Powassan virus, Bartonella spp., and Babesia spp. were not found. Analysis of the genetic diversity of revealed pathogens demonstrated that TBEV strains belonged to the Siberian and Far-Eastern subtypes, and the Far-Eastern subtype of TBEV is most frequently found in urban biotopes (up to 43% of urban strains of TBEV). WNV strains belonged to the 1a genotype. Borrelia spp. was classified as B. garinii, Rickettsia spp. was classified as R. tarasevichiae and probably as a new Rickettsia raoultii subspecies, and Ehrlichia spp. was classified as E. muris. The coexistence of several pathogens was found in 5.7% of tick specimens, and TBEV + Borrelia spp. was the most frequent combination.     

Two new records of Telenominae (Hymenoptera, Scelionidae) from the Rovno amber (Eocene of Ukraine)

Two new scelionid species of the subgenus Telenomus, genus Telenomus, subfamily Telenominae are described: Telenomus (Telenomus) oculus sp. nov. and T. (T.) tetragonus sp. nov. Brief morphological characterizations of the new taxa are given, and comparative analysis of the inclusions described and members of the recent fauna is provided.     

Tsutsugamushi fever in the Kuril Islands]

The authors present the results of a 6-year study of tsutsugamushi fever at the Kuril islands. The area of the disease proved to include Southern Kuril islands - Shikotan and Kunashir. The principal natural carriers of tsutsugamushi among the mouse-like rodents and trombiculidae larvae were revealed; highly virulent strains were found to prevail among the tsutsugamushi rickettsia strains. Tsutsugamushi fever in the population is characterized by a benign course, pyrexia, primary affects and lymphadenitis.