Aim: In this study, our goal was to study the inhibition of nicotine metabolism by P450 2A6, as a means for reduction in tobacco use and consequently the prevention of smoking-related cancers. Nicotine, a phytochemical, is an addictive stimulant, responsible for the tobacco-dependence in smokers. Many of the other phytochemicals in tobacco, including polycyclic aromatic hydrocarbons, N-nitrosamines, and aromatic amines, are potent systemic carcinogens. Tobacco smoking causes about one of every five deaths in the United States annually. Nicotine plasma concentration is maintained by the smokers' smoking behavior within a small range. Nicotine is metabolized by cytochrome P450s 2A6 and 2A13 to cotinine. This metabolism causes a decrease in nicotine plasma levels, which in turn leads to increased tobacco smoking, and increased exposure to the tobacco carcinogens.Methods: Using the phytochemical nicotine as a lead structure, and taking its interactions with the P450 2A6 binding pocket into consideration, new pyridine derivatives were designed and synthesized as potential selective mechanism-based inhibitors for this enzyme.
Results:The design and synthesis of two series of novel pyridine-based compounds, with varying substituents and substitution locations on the pyridine ring, as well as their inhibitory activities on cytochrome P450 2A6 and their
Conclusion:The pyridine compounds with an imidazole or propargyl ether containing substituent on position 3 were found to be promising lead compounds for further development. Hydrogen-bonding interactions were determined to be crucial for effective binding of these molecules within the P450 2A6 active site.
In the title flavonoid derivative, C19H16O5, the chromene portion is planar (r.m.s. deviation = 0.022 Å) with the substituents lying closely to the same plane. The dihedral angle between its mean plane and that of the benzene ring is 4.9 (1)°. This planarity is due, in part, to the presence of a strong intramolecular C—H⋯O hydrogen bond and to two weak C—H⋯O contacts. In the crystal, neighboring molecules are linked by a C—H⋯O hydrogen bond and a C—H⋯π interaction, forming chains along the a-axis direction.
The title compound, C17H18O2, crystallizes in two-dimensional sheets, in which the 2-(pentyloxy)dibenzo[b,d]furan molecules are arranged in a head-to-head and tail-to-tail fashion that enables hydrophobic interactions between fully extended 2-pentoxy chains and π–π stacking between dibenzofuran rings in adjacent rings. Nearest intermolecular π-π stacking contacts are 3.3731 (12) Å. The molecule is nearly planar with an r.m.s. deviation of 0.0803 Å from the mean plane defined by the nineteen non-hydrogen atoms.
We report here the complete genome sequences of four subcluster L3 mycobacteriophages newly isolated from soil samples, using Mycobacterium smegmatis mc2155 as the host. Comparative genomic analyses with four previously described subcluster L3 phages reveal strong nucleotide similarity and gene conservation, with several large insertions/deletions near their right genome ends.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.