Synthesis of a 5,6-Dihydropyran-2-one Derivative with Dual Anti-Cell-Migration and Anticancer Activity

Abstract

The 5,6-dihydropyran-2-one scaffold is found in several biologically active compounds. In this study, we synthesized a new derivative, named PY801. This compound (1 µM) was shown to suppress the migration of lung cancer cells. Furthermore, in cancer cell line panel experiments, PY801 showed cytotoxicity against several specific cell lines. The IC₅₀ values of PY801 against colorectal cancer cells HCT116 and breast cancer cells MCF7 were determined to be 8.9 and 9.3 µM, respectively; these values are lower than those of the anticancer drug cisplatin. Compared with the IC₅₀ against peripheral blood mononuclear cells (PBMC) from a healthy donor, the selectivity index was determined to be >7. This study showed PY801 might be a new lead compound for anti-cell-migration and anticancer drugs.

Key words

dihydropyran-2-ones - anti-cell-migration activity - anticancer drugs

Publication History

Received: 27 February 2025

Accepted after revision: 28 April 2025

Accepted Manuscript online:
28 April 2025

Article published online:
16 June 2025

• References and Notes

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• 26 Benzyl 2-[(2R)-6-Oxo-3,6-dihydro-2H-pyran-2-yl]ethyl Propane-1,3-diylbiscarbamate (PY801) Amine 11 (406 mg, 1.95 mmol) was added to a solution of carbonate 8 (400 mg, 1.30 mmol) in DMSO (5 mL), and the mixture was stirred for 5 h under argon. H₂O (30 mL) was then added, and the mixture was extracted with CH₂Cl₂ (3 × 30 mL). The combined organic phase was dried (Na₂SO₄) and concentrated under a vacuum. The crude product was purified by column chromatography [silica gel, hexane–EtOAc (8:2)] to give white powder; yield: 411 mg (84%). ¹H NMR (600 MHz, CDCl₃): = 7.31–7.23 (m, 5 H), 6.83–6.79 (m, 1 H), 5.96 (dd, J = 9.7, 1.3 Hz, 1 H), 5.10 (d, J = 20.3 Hz, 2 H), 5.03 (s, 2 H), 4.50 (dt, J = 12.0, 4.6 Hz, 1 H), 4.22–4.12 (m, 2 H), 3.20–3.12 (m, 4 H), 2.34–2.25 (m, 2 H), 2.02 (dd, J = 13.9, 7.7 Hz, 1 H), 1.92 (dd, J = 13.0, 5.7 Hz, 1 H), 1.78–1.31 (m, 2 H). ¹³C NMR (150 MHz, CDCl₃): = 164.01, 156.93, 156.66, 144.80, 136.55, 128.54, 128.14, 128.03, 121.52, 74.92, 66.75, 60.46, 37.66, 37.56, 34.46, 30.42, 29.37. HRMS (FAB): m/z [M + Na]⁺ calcd for C₁₉H₂₄N₂NaO₆: 399.1532; found: 399.1537.