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, Inhaltsverzeichnis

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

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

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Abstract

Alle Artikel dieser Rubrik

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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Referenzen

References and Notes
1 Current address: College of Pharmacy, University of Florida, FL, USA
2 Eskandari K, Rafieian-Kopaei M. Chem. Heterocycl. Compd. 2016; 52: 158
3 Meragelman TL, Scudiero DA, Davis RE, Staudt LM, McCloud TG, Cardellina JH. II, Shoemaker RH. J. Nat. Prod. 2009; 72: 336
4 Grover A, Agrawal V, Shandilya A, Bisaria VS, Sundar DI. BMC Bioinf. 2011; 12 (Suppl. 13) S22
5 BouzBouz S, Cossy J. Org. Lett. 2003; 5: 1995
6 Sassa T, Kato H, Kajiura H. Tetrahedron Lett. 1986; 27: 2121
7 Goswami A, Saikia PP, Saikia B, Chaturvedi D, Barua NC. Tetrahedron Lett. 2011; 52: 5133
8 Smith TE, Djang M, Velander AJ, Downey CW, Carroll KA, van Alphen S. Org. Lett. 2004; 6: 2317
9 Wang F.-D, Yue J.-M. Synlett 2005; 2077
10 Yadav J, Ather H, Rao NV, Reddy MS, Prasad A. Synlett 2010; 1205
11 Carré G, Carreyre H, Ouedraogo M, Becq F, Bois P, Thibaudeau S, Vandebrouck C, Bescond J. Eur. J. Pharmacol. 2014; 728: 119
12 Li H, Tatlock J, Linton A, Gonzalez J, Jewell T, Patel L, Ludlum S, Drowns M, Rahavendran SV, Skor H, Hunter R, Shi ST, Herlihy KJ, Parge H, Hickey M, Yu X, Chau F, Nonomiya J, Lewis C. J. Med. Chem. 2009; 52: 1255
13 Gan W, He M, Huang Y, Dai Z, Yu M, Lu Y, Wang Y, Han X, Zeng X. Org. Lett. 2024; 26: 10114
14 Hamdy AK, Sakamoto T, Toma T, Sakamoto M, Abourehab MA. S, Otsuka M, Fujita M, Tateishi H, Radwan MO. Pharmaceuticals 2022; 15: 1579
15 Avula SK, Das B, Csuk R, Al-Rawahi A, Al-Harrasi A. Molecules 2020; 25: 1905
16 Marco JA, Carda M, Murga J, Falomir E. Tetrahedron 2007; 63: 2929
17 Neumaier J, Maier ME. Synlett 2011; 187
18 Wender PA, Baryza JL, Brenner SE, DeChristopher BA, Loy BA, Schrier AJ, Verma VA. Proc. Natl. Acad. Sci. U. S. A. 2011; 108: 6721
19 Shinde DB, Kanth BS, Satyakumar A, Kamble V, Das B. Lett. Org. Chem. 2013; 10: 317
20 Ding F, Jennings MP. J. Org. Chem. 2008; 73: 5965
21 Pardo LM, Tellitu I, Domínguez E. Tetrahedron 2010; 66: 5811
22 Kamo M, Ito M, Toma T, Gotoh H, Shimozono R, Nakagawa R, Koga R, Monde K, Tateishi H, Misumi S, Otsuka M, Fujita M. Bioorg. Chem. 2021; 107: 104627
23 https://dtp.cancer.gov/discovery_development/nci-60/methodology.htm (accessed 8 December 2024).
24 Sakamoto M, Kai S, Tateishi H, Biswas T, Sakamoto T, Teshima M, Iwanaga M, Nishikawa A, Sakamoto A, Shimozono R. Synlett. in press, DOI:
25 Toma T, Tateishi H, Kawakami K, Ali TF, Kamo M, Monde K, Nakashima Y, Fujita M, Otsuka M. Int. J. Mol. Sci. 2022; 23: 5047
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.

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