Diet and subsistence in Bronze Age pastoral communities from the southern Russian steppes and the North Caucasus.

The flanks of the Caucasus Mountains and the steppe landscape to their north offered highly productive grasslands for Bronze Age herders and their flocks of sheep, goat, and cattle. While the archaeological evidence points to a largely pastoral lifestyle, knowledge regarding the general composition of human diets and their variation across landscapes and during the different phases of the Bronze Age is still restricted. Human and animal skeletal remains from the burial mounds that dominate the archaeological landscape and their stable isotope compositions are major sources of dietary information.

Synthesis, biological evaluation, and molecular modeling of 11H-indeno[1,2-b]quinoxalin-11-one derivatives and tryptanthrin-6-oxime as c-Jun N-terminal kinase inhibitors.

c-Jun N-terminal kinases (JNKs) play a central role in many physiologic and pathologic processes. We synthesized novel 11H-indeno[1,2-b]quinoxalin-11-one oxime analogs and tryptanthrin-6-oxime (indolo[2,1-b]quinazoline-6,12-dion-6-oxime) and evaluated their effects on JNK activity. Several compounds exhibited sub-micromolar JNK binding affinity and were selective for JNK1/JNK3 versus JNK2.

Virtual screening, synthesis and biological evaluation of DNA intercalating antiviral agents.

This paper describes computer-aided design of new anti-viral agents against Vaccinia virus (VACV) potentially acting as nucleic acid intercalators. Earlier obtained experimental data for DNA intercalation affinities and activities against Vesicular stomatitis virus (VSV) have been used to build, respectively, pharmacophore and QSAR models. These models were used for virtual screening of a database of 245 molecules generated around typical scaffolds of known DNA intercalators.

Anti-Inflammatory Effects and Joint Protection in Collagen-Induced Arthritis after Treatment with IQ-1S, a Selective c-Jun N-Terminal Kinase Inhibitor.

c-Jun N-terminal kinases (JNKs) participate in many physiologic and pathologic processes, including inflammatory diseases. We recently synthesized the sodium salt of IQ-1S (11H-indeno[1,2-b]quinoxalin-11-one oxime) and demonstrated that it is a high-affinity JNK inhibitor and inhibits murine delayed-type hypersensitivity. Here we show that IQ-1S is highly specific for JNK and that its neutral form is the most abundant species at physiologic pH.

Dose-dependent IFN-stimulating and immunomodulating properties of 6H-indolo[2,3-B] quinoxaline derivatives.

Two 6H-indoloquinoxaline derivatives were studied in different doses and schemes of application for their INFgamma-inducing potential and ability to effect functional activity of phagocytic cells. Tested compounds were shown to possess comparable or higher activity than reference drug Amixin in analogous doses. One indoloquinoxaline significantly elevated metabolic activity of macrophages and increased their potential for phagocytosis.

Synthesis and biological activity of 7H-benzo[4,5]indolo[2,3-b]-quinoxaline derivatives.

New 7-(2-aminoethyl)-7H-benzo[4,5]indolo[2,3-b]quinoxalines (13-20) were synthesized with high yields starting from 3H-benzo[e]indole-1,2-dione. These compounds were screened for the cytotoxicity, anti-viral activity, interferon inducing ability and DNA affinity compared with the corresponding 6-(2-aminoethyl)-6H-indolo[2,3-b]quinoxaline derivatives (1-12). It was shown, that compounds 13-20 bind to DNA stronger (lg Кa=6.

Synthesis, cytotoxicity, antiviral activity and interferon inducing ability of 6-(2-aminoethyl)-6H-indolo[2,3-b]quinoxalines.

New 6-(2-aminoethyl)-6H-indolo[2,3-b]quinoxalines were synthesized with high yields using bromoethylisatin and 6-(2-bromoethyl)-6H-indolo[2,3-b]quinoxaline as intermediates. These compounds were screened for the cytotoxicity, antiviral activity and interferon inducing ability. It was shown, that tested 6-(2-aminoethyl)-6H-indolo[2,3-b]quinoxalines are low toxic potent interferon inducers and antivirals.

Synthesis and affinity to DNA of phenylbenzoimidazoles and benzoimidazo[1,2-c]quinazolines.

Novel N-(benzoimidazophenyl)dialkylaminoalkylamides and 6-dialkylaminoalkylbenzoimidazo[1,2-c]quinazolines were prepared as potential interferon inducers and antiviral agents. They were screened for the DNA affinity by the ethidium bromide displacement assay. It was shown that the lg K(a) values of the compounds containing tetracyclic benzoimidazo[1,2-c]quinazoline fragment are approximately one order magnitude greater than those of the corresponding acyclic phenylbenzoimidazole derivatives.

Biological active acridine derivatives. Part 4: Synthesis and antiviral activity of some bis-acridinylated diamides.

Nine bis-acridine derivatives have been synthesized in search of structures with antiviral properties. Synthesis of target compounds was provided by a standard peptide-like coupling procedure using aliphatic diamines and protected amino acids following protective group removing and acridinylation by means of 9-methoxyacridine. Two out of nine compounds tested demonstrate high protective activity of Vero cells against HSV infection.