| Literature DB >> 33647840 |
Shruti Choudhary1, Arpit Doshi1, Lerin Luckett-Chastain2, Michael Ihnat2, Ernest Hamel3, Susan L Mooberry4, Aleem Gangjee5.
Abstract
The efficacy of quinazoline-based antiglioma agents has been attributed to their effects on microtubule dynamics.1,2 The design, synthesis and biological evaluation of quinazolines as potent inhibitors of multiple intracellular targets, including microtubules and multiple RTKs, is described. In addition to the known ability of quinazolines 1 and 2 to cause microtubule depolymerization, they were found to be low nanomolar inhibitors of EGFR, VEGFR-2 and PDGFR-β. Low nanomolar inhibition of EGFR was observed for 1-3 and 9-10. Compounds 1 and 4 inhibited VEGFR-2 kinase with activity better than or equal to that of sunitinib. In addition, compounds 1 and 2 had similar potency to sunitinib in the CAM angiogenesis assay. Multitarget activities of compounds in the present study demonstrates that the quinazolines can affect multiple pathways and could lead to these agents having antitumor potential caused by their activity against multiple targets.Entities:
Keywords: Angiogenesis; Microtubule targeting agents; Multi-target inhibitors; Quinazolines; Receptor tyrosine kinase
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Year: 2021 PMID： 33647840 PMCID： PMC7995636 DOI： 10.1016/j.bmc.2021.116061
Source DB: PubMed Journal: Bioorg Med Chem ISSN： 0968-0896 Impact factor: 3.641