Background: As reported EGFR is a sialoglycoprotein with tyrosine kinase activity
involved in control of cellular survival, multiplication, differentiation and metastasis. Dysregulation
or aberrant expression of EGFR has been implicated in cell transformation and having oncogenic
roles in a number of human cancers. Therefore EGFR has become a significant target for developing
targeted therapy for cancer.
Methods: A novel series of indole-3-carboxamide derivatives as EGFR inhibitors were designed,
synthesized and evaluated for the anticancer activity in vitro against three EGFR high-expressed
cancer cell lines (A549, HeLa, and SW480), one EGFR low-expressed cell line (HepG2) and one
human liver normal cell line (HL7702) by MTT assay.
Results: The target compounds 6c, 6f, 6i, 6j, 6l, 6r, 6u and 6x exhibited potent anticancer activities
against the three tested cancer cell lines and weak cytotoxic effects on HepG2, which imply that the
target compounds are probably effective in inhibiting EGFR. And they also did not show measurable
activities in HL7702, which imply the target compounds are likely to overcome the nonspecific
toxicity against normal cells. Particularly, the target compound 6x indicated equal to the positive
control erlotinib. In addition, molecular docking studies demonstrated the target compound 6x may
be the potential inhibitor to EGFR.
Conclusion: A new EGFR inhibitor scaffold and a preliminary discussion on their SARs provide
promising opportunities to guide further research on indole-3-carboxamide derivatives as novel