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

Ahmed K. Hamdy; Hiroshi Araki; Hiroshi Tateishi; Tsugumasa Toma; Mohamed O. Radwan; Shashwata Biswas; Takeo Kuwata; Shuzo Matsushita; Mikako Fujita; Shin-ichiro Niwa; Masami Otsuka

doi:10.1055/a-2595-7004

Synlett, Table of Contents

Synlett 2025; 36(16): 2585-2590
DOI: 10.1055/a-2595-7004

letter

Small Molecules in Medicinal Chemistry

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

Authors

Ahmed K. Hamdy∗

^aMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan

^bCollaborative Research Program with the Chemo-Sero-Therapeutic Research Institute for Anti-viral Agents and Hematological Diseases, Joint Research Center for Human Retrovirus Infection, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan

^cDepartment of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt
Hiroshi Araki

^dLink Genomics Ltd., 7-1 Kobunacho, Nihonbashi, Chuo-ku, Tokyo 103-0024, Japan
Hiroshi Tateishi

^aMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
Tsugumasa Toma

^aMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
Mohamed O. Radwan

^aMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
Shashwata Biswas

^bCollaborative Research Program with the Chemo-Sero-Therapeutic Research Institute for Anti-viral Agents and Hematological Diseases, Joint Research Center for Human Retrovirus Infection, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
Takeo Kuwata

^bCollaborative Research Program with the Chemo-Sero-Therapeutic Research Institute for Anti-viral Agents and Hematological Diseases, Joint Research Center for Human Retrovirus Infection, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
Shuzo Matsushita

^bCollaborative Research Program with the Chemo-Sero-Therapeutic Research Institute for Anti-viral Agents and Hematological Diseases, Joint Research Center for Human Retrovirus Infection, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
Mikako Fujita

^aMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
Shin-ichiro Niwa

^dLink Genomics Ltd., 7-1 Kobunacho, Nihonbashi, Chuo-ku, Tokyo 103-0024, Japan
Masami Otsuka∗

^aMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan

^eScience Farm Ltd., 1-7-30 Kuhonji, Chuo-ku, Kumamoto 862-0976, Japan

Abstract

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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

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References

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.

Supplementary Material

Supporting Information (PDF)