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.
View Article and Find Full Text PDFMany evidences suggest that DNA-drug interaction in the minor groove and the intercalation of drugs into DNA may play critical roles in antiviral, antimicrobial, and antitumor activities. As a continuous effort to develop novel antiviral agents, the series of planar fluorenone (3a-7d) were synthesized and used along with nonplanar biphenyls (11a-d) for the comparative analysis of their interaction with DNA. The chemical structure of new compounds was confirmed by H NMR, C NMR and mass spectra as well as elemental analysis.
View Article and Find Full Text PDFEur J Med Chem
January 2019
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.
View Article and Find Full Text PDFThis 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.
View Article and Find Full Text PDFc-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.
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