2. Academic Validation
  3. Potential of substituted quinazolines to interact with multiple targets in the treatment of cancer

Potential of substituted quinazolines to interact with multiple targets in the treatment of cancer

  • Bioorg Med Chem. 2021 Apr 1:35:116061. doi: 10.1016/j.bmc.2021.116061.
Shruti Choudhary 1,  Arpit Doshi 1,  Lerin Luckett-Chastain 2,  Michael Ihnat 2,  Ernest Hamel 3,  Susan L Mooberry 4,  Aleem Gangjee 5
Affiliations

Affiliations

  • 1 Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, 600 Forbes Avenue, Pittsburgh, PA 15282, United States.
  • 2 College of Pharmacy, University of Oklahoma Health Science Center, 1110 North Stonewall, Oklahoma City, OK 73117, United States.
  • 3 Molecular Pharmacology Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, United States.
  • 4 Department of Pharmacology, Mays Cancer Center, University of Texas Health Science Center, San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, United States.
  • 5 Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, 600 Forbes Avenue, Pittsburgh, PA 15282, United States. Electronic address: gangjee@duq.edu.
PMID: 33647840 DOI: 10.1016/j.bmc.2021.116061
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.

Keywords

Angiogenesis; Microtubule targeting agents; Multi-target inhibitors; Quinazolines; Receptor tyrosine kinase.

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