The human liver cytochrome P450 (CYP) 2A6 and the respiratory CYP2A13 enzymes play role in nicotine metabolism and activation of tobacco-specific nitrosamine carcinogens. Inhibition of both enzymes could offer a strategy for smoking abstinence and decreased risks of respiratory diseases and lung cancer. In this study, activity-guided isolation identified four flavonoids 1-4 (apigenin, luteolin, chrysoeriol, quercetin) from Vernonia cinerea and Pluchea indica, four hirsutinolide-type sesquiterpene lactones 5-8 from V. cinerea, and acetylenic thiophenes 9-11 from P. indica that inhibited CYP2A6- and CYP2A13-mediated coumarin 7-hydroxylation. Flavonoids were most effective in inhibition against CYP2A6 and CYP2A13, followed by thiophenes, and hirsutinolides. Hirsutinolides and thiophenes exhibited mechanism-based inhibition and in irreversible mode against both enzymes. The inactivation kinetic K values of hirsutinolides against CYP2A6 and CYP2A13 were 5.32-15.4 and 0.92-8.67 µM, respectively, while those of thiophenes were 0.11-1.01 and 0.67-0.97 µM, respectively.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6009911 | PMC |
| http://dx.doi.org/10.1080/14756366.2017.1363741 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Synthesis and Antiviral Evaluation of 5-(4-Aryl-1,3-butadiyn-1-yl)-uridines and Their Phosphoramidate Pronucleotides.
Molecules
December 2024
Institute of Organic and Analytical Chemistry (ICOA UMR 7311), CNRS, University of Orleans, F-45067 Orléans, France.
The emergence of RNA viruses driven by global population growth and international trade highlights the urgent need for effective antiviral agents that can inhibit viral replication. Nucleoside analogs, which mimic natural nucleotides, have shown promise in targeting RNA-dependent RNA polymerases (RdRps). Starting from protected 5-iodouridine, we report the synthesis of -substituted-(1,3-diyne)-uridines nucleosides and their phosphoramidate prodrugs.
View Article and Find Full Text PDFDivergent Access to Polycyclic Fluorenofuran Systems via Palladium-Catalyzed Cascade Furan-Participated Diels-Alder Cycloaddition Reactions.
Org Lett
December 2024
State Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemical Engineering, Nanjing Tech University, Nanjing 211800, China.
The Pd-catalyzed reaction of 1-(2-iodophenyl)-3-arylprop-2-yn-1-ones with benzene-tethered furan-ynes produces novel fused hexacyclic indenone-furan scaffolds, while the reaction with propargyl furfuryl ethers affords the pentacyclic indenone-spirodifuran system. The thiophene-containing alkynes also proceed by similar transformations. A mechanism involving the Pd-catalyzed coupling and propargylic Alder-ene reaction to generate the indenone-allene intermediate, followed by an intramolecular furan/thiophene-participated inverse electron-demand Diels-Alder reaction, is proposed.
View Article and Find Full Text PDFThieno[3,2-]thiophene for the Construction of Far-Red Molecular Rotor Hemicyanines as High-Affinity DNA Aptamer Fluorogenic Reporters.
Anal Chem
October 2024
Departments of Chemistry and Toxicology, University of Guelph, Guelph, Ontario N1G 2W1, Canada.
The construction of far-red fluorescent molecular rotors (FMRs) is an imperative task for developing nucleic acid stains that have superior compatibility with cellular systems and complex matrices. A typical strategy relies on the methine extension of asymmetric cyanines, which unfortunately fails to produce sensitive rotor character. To break free from this paradigm, we have synthesized far-red hemicyanines using a dimethylamino thieno[3,2-]thiophene donor.
View Article and Find Full Text PDFKey role of cycloalkyne nature in alkyne-dye reagents for enhanced specificity of intracellular imaging by bioorthogonal bioconjugation.
Org Biomol Chem
September 2024
Institute of Chemistry, Saint Petersburg State University (SPbU), Saint Petersburg, 199034, Russia.
Article Synopsis
- Researchers created conjugates of a specific compound (benzothiophene-fused azacyclononyne BT9N-NH2) with fluorescent dyes to visualize azidoglycans inside cells.
- The importance of the cycloalkyne core was shown by comparing the new reagents to existing DBCO- and BCN-dye conjugates.
- To enhance specificity during bioconjugation within cells, the study suggests using the less reactive BT9N-dye reagents instead of the more reactive DBCO- and BCN-dye conjugates.
Reaction dynamics of S(P) with 1,3-butadiene and isoprene: crossed-beam scattering, low-temperature flow experiments, and high-level electronic structure calculations.
Faraday Discuss
August 2024
Department of Chemistry, University of Missouri, Columbia, MO 65211, USA.
Sulfur atoms serve as key players in diverse chemical processes, from astrochemistry at very low temperature to combustion at high temperature. Building upon our prior findings, showing cyclization to thiophenes following the reaction of ground-state sulfur atoms with dienes, we here extend this investigation to include many additional reaction products, guided by detailed theoretical predictions. The outcomes highlight the complex formation of products during intersystem crossing (ISC) to the singlet surfaces.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!