Design, synthesis and biological evaluation of novel heptamethine cyanine dye-erlotinib conjugates as antitumor agents.

In this study, in order to improve the tumor cell targeting ability of EGFR-TKI, EGFR-TKI erlotinib was conjugated with the cancer cell-targeting heptamethine cyanine dyes to form seventeen novel erlotinib-dye conjugates. The efficiency of tumor targeting properties of conjugates against cancer cell growth and EGFR-TK inhibition was evaluated in vitro. The result revealed that most erlotinib-dye conjugates exhibited stronger inhibitory effect on A549, H460, H1299 and MDA-MB-231 cell lines than the parent drug erlotinib. Meanwhile, representative compounds exhibited weak cytotoxicity on human normal mammary epithelial MCF-10A cells. Moreover, the conjugate CE17 also showed ∼14-fold higher EGFR-TK inhibition activity (IC50=0.124 μM) than erlotinib (IC50=5.182 μM) in A549 cell line. Finally, molecular docking analysis verified that the erlotinib moiety of compound CE17 could form hydrogen bond with Met-769 and occupy active cavity of EGFR-TK. Therefore, we believed the integration strategy between heptamethine cyanine dyes and EGFR-TKI will contribute to enhancing the therapeutic effect of EGFR-TKI for NSCLC treatment. PMID: 32949719 [PubMed - as supplied by publisher]
Source: Bioorganic and Medicinal Chemistry Letters - Category: Chemistry Authors: Tags: Bioorg Med Chem Lett Source Type: research