Synthesis of scaberol C amino acid ester derivatives with anti-cancer activity

Abstract

A series of amino acid ester trifluoroacetate derivatives was synthesized from scaberol C. They were screened for their inhibitory activity against Non-Small Cell Lung Cancer (NSCLC) cells. Among them, compound 2 l showed significant cytotoxicity against A549 and H460 cells (IC₅₀), and was more active than cisplatin (DDP). The epidermal growth factor receptor (EGFR) was overexpressed in NSCLC, which was the target of multiple cancer therapies and a strong prognostic indicator. Our previous studies reported that the target of scaberol C derivatives against NSCLC cells was EGFR. And then molecular docking analysis and molecular dynamics (MD) simulations indicated that 2 l can stably and covalently bind to the EGFR target protein.

Keywords:

• scaberol C derivatives
• NSCLC
• EGFR
• molecular docking
• molecular dynamics simulations

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the [National Natural Science Foundation of China #1] under Grant [number 81903511]; [China Postdoctoral Science Foundation #2] under Grant [number 2019M661133]; [Scientific Research Fund Project of Liaoning Provincial Department of Education #3] under Grant [number LJKZ0912]; [Shenyang Pharmaceutical University Excellent Youth Lift Plan #4] under Grant [number YQ202202]; [Natural Science Foundation of Liaoning Province #5] under Grant [number 2022-MS-244]; and [Shenyang Pharmaceutical University innovation and entrepreneurship training program #6] under Grant [number 202310163040].