Quinazolinone-Amino Acid Hybrids as Dual Inhibitors of EGFR Kinase and Tubulin Polymerization

Mohamed Zayed, Heba Rateb, Sahar Ahmed, Osama Khaled, Sabrin Ibrahim
2018 Molecules  
Some fluoroquinazolinones (A–H) were designed, synthesized and biologically evaluated for their antitumor activity against the two cell lines, MCF-7 and MDA-MBA-231. New derivative G (IC50 = 0.44 ± 0.01 µM) showed antitumor activity, better than that of the reference drug erlotinib (IC50 = 1.14 ± 0.04 µM) against MCF-7. New derivative E (IC50 = 0.43 ± 0.02 µM) showed higher activity than the reference drug erlotinib (IC50 = 2.55 ± 0.19 µM) against MDA-MBA-231. Furthermore, the EGFR (epidermal
more » ... owth factor receptor) and tubulin inhibition assays were carried out for the highest active derivatives to reveal the expected mechanism of action. They exhibited significant results compared to the reference drugs. Molecular docking simulations were performed on EGFR and tubulin binding sites to rationalize the experimental results and describe their binding modes. The results of the molecular modeling study were correlated with that of the antitumor screening.
doi:10.3390/molecules23071699 pmid:30002297 fatcat:zsxtqovbd5ex5cqgra4xdhffeq