4 years ago

Discovery of Benzo[g]quinazolin benzenesulfonamide derivatives as dual EGFR/HER2 inhibitors

Discovery of Benzo[g]quinazolin benzenesulfonamide derivatives as dual EGFR/HER2 inhibitors
An array of some new N-(substituted)-2-((4-oxo-3-(4-sulfamoylphenyl)-3,4-dihydrobenzo[g]quinazolin-2-yl)thio)acetamide 5–19 were synthesized from the starting compound 4-(2-mercapto-4-oxobenzo[g]quinazolin-3(4H)-yl)benzenesulfonamide 4, to be assessed for their cytotoxic activity against A549 lung cancer cell line and to determine their inhibitory effect on EGFR tyrosine kinase enzyme. Compounds 5–19 showed high activity towards A549 cell line with IC50 values of 0.12–8.70 μM. Compounds 6, 12 and 18 were the most potent in this series. These compounds were further screened as dual inhibitors for EGFR/HER2 enzymes in comparison with erlotinib and were found to possess very potent activity. Compound 12 showed the highest activity with IC50 values of 0.06 μM and 0.30 μM towards EGFR and HER2, respectively. Accordingly, the apoptotic effect of the most potent compounds 6, 12 and 18 was investigated and showed a marked increase in the level of caspases-3 by 6, 9 and 8 folds, respectively, compared to the control cells. Moreover, Molecular modeling was performed inside the active site of EGFR, keeping in mind their binding possibilities, bond lengths, angles and energy scores. It was found that the most active compounds demonstrated the best binding scores in the active site of EGFR, which may clarify their high inhibition profile.

Publisher URL: www.sciencedirect.com/science

DOI: S0223523417307766

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.