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DOI: https://doi.org/10.6023/cjoc202601044

ARTICLE

Synthesis, anticancer evaluation, and preliminary mechanism study of 1,3,4-oxadiazole derivatives targeting K562 tumor cells

  • Wu Yueyou ,
  • He Dandan ,
  • Feng Nianlin ,
  • Zhang Yi ,
  • Liu Dandan ,
  • Zhou Yue ,
  • Li Chenchen ,
  • Wang Zhenchao
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  • aSchool of Pharmaceutical Sciences, Guizhou University, Guiyang, Guizhou 550025;
    bState Key Laboratory of Green Pesticides, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang, Guizhou 550025

Received date: 2026-03-24

  Revised date: 2026-05-26

  Online published: 2026-06-26

Supported by

We gratefully acknowledge financial support from the National Natural Science Foundation of China (Grant No. 32360689), the Guizhou Provincial Foundation for Excellent Scholars Program (Project No. GCC[2023]072), the National Key Research and Development Program of China (Grant No. 2023YFD1400400), and the Youth Guidance Project of the Guizhou Provincial Basic Research Program (Natural Science) (Grant No. QN[2025]010, QN[2025]009).

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Abstract

Chronic myeloid leukemia (CML) is a hematological malignancy characterized by abnormal myeloid cell proliferation, and the emergence of drug resistance to conventional tyrosine kinase inhibitors necessitates novel antitumor agents. In this study, we synthesized 30 novel hybrid derivatives incorporating indole, 1,3,4-oxadiazole, and benzenesulfonamide scaffolds—pharmacophores recognized for antitumor potential—aiming to enhance activity and selectivity. Among these compounds, XL-10 demonstrated potent antiproliferative effects against CML K562 cells, exhibiting an IC₅₀ value of 6.69 ± 0.35 μM. Mechanistic investigations revealed that XL-10 induces apoptosis in K562 cells by disrupting redox homeostasis, as evidenced by elevated reactive oxygen species (ROS) levels and reduced mitochondrial membrane potential. Flow cytometry analysis indicated that XL-10 arrests K562 cells at the G2/M phase through regulation of key cell cycle proteins including Cyclin B1 and CDK1, while Western blot assays confirmed its modulation of the MAPK and PI3K-AKT signaling pathways. These findings elucidate the antitumor mechanisms of XL-10 and highlight its potential as a promising lead compound for the development of targeted CML therapies.

Key words： K562 cells; anticancer activity; nitrogen-containing heterocycles; chronic myeloid leukemia; 1,3,4-oxadiazole

Cite this article

Wu Yueyou , He Dandan , Feng Nianlin , Zhang Yi , Liu Dandan , Zhou Yue , Li Chenchen , Wang Zhenchao . Synthesis, anticancer evaluation, and preliminary mechanism study of 1,3,4-oxadiazole derivatives targeting K562 tumor cells[J]. Chinese Journal of Organic Chemistry, 0 : 0 . DOI: 10.6023/cjoc202601044

References

[1] Soverini, S.; Mancini, M.; Bavaro, L.; Cavo, M.; Martinelli, G. Mol Cancer. 2018, 17, 49.
[2] Cortes, J.; Pavlovsky, C.; Saußele, S. The Lancet. 2021, 398, 1914-1926.
[3] Braun, T. P.; Eide, C. A.; Druker, B. J. Cancer Cell. 2020, 37, 530-542.
[4] Hochhaus, A.; Larson, R. A.; Guilhot, F.; Radich, J. P.; Branford, S.; Hughes, T. P.; Baccarani, M.; Deininger, M. W.; Cervantes, F.; Fujihara, S.; Ortmann, C.; Menssen, H. D.; Kantarjian, H.; O, B. S. G.; Druker, B. J. N Engl J Med. 2017, 376, 917-927.
[5] Shah, N. P.; Tran, C.; Lee, F. Y.; Chen, P.; Norris, D.; Sawyers, C. L. Science. 2004, 305, 399-401.
[6] Atallah, E.; Schiffer, C. A.; Radich, J. P.; Weinfurt, K. P.; Zhang, M.; Pinilla-Ibarz, J.; Kota, V.; Larson, R. A.; Moore, J. O.; Mauro, M. J.; Deininger, M. W. N.; Thompson, J. E.; Oehler, V. G.; Wadleigh, M.; Shah, N. P.; Ritchie, E. K.; Silver, R. T.; Cortes, J.; Lin, L.; Visotcky, A.; Baim, A.; Harrell, J.; Helton, B.; Horowitz, M.; Flynn, K. E. JAMA Oncol. 2021, 7, 42-50.
[7] Jabbour, E.; Kantarjian, H. Am J Hematol. 2020, 95, 691-709.
[8] Osman, A. E. G.; Deininger, M. W. Blood Rev. 2021, 49, 100825.
[9] Kamal, A.; Surendranadha Reddy, J.; Janaki Ramaiah, M.; Dastagiri, D.; Vijaya Bharathi, E.; Ameruddin Azhar, M.; Sultana, F.; Pushpavalli, S. N. C. V.; Pal-Bhadra, M.; Juvekar, A.; Sen, S.; Zingde, S. Eur J Med Chem. 2010, 45, 3924-3937.
[10] Asati, V.; Bhupal, R.; Bhattacharya, S.; Kaur, K.; Gupta, G. D.; Pathak, A.; Mahapatra, D. K. Anticancer Agents Med Chem. 2023, 23, 404-416.
[11] Olgen, S.; Kaleli, S. N. B.; Karaca, B. T.; Demirel, U. U.; Bristow, H. K. Curr Med Chem. 2024, 31, 3798-3817.
[12] Cros, S.; Wright, M.; Morimoto, M.; Lataste, H.; Couzinier, J. P.; Krikorian, A. Semin Oncol. 1989, 16, 15-20.
[13] Anderson, R.; Makvandi, M.; Xu, K.; Lieberman, B. P.; Zeng, C.; Pryma, D. A.; Mach, R. H. Nucl Med Biol. 2016, 43, 752-758.
[14] Prieto-Domínguez, N.; Méndez-Blanco, C.; Carbajo-Pescador, S.; Fondevila, F.; García-Palomo, A.; González-Gallego, J.; Mauriz, J. L. Oncotarget. 2017, 8, 85858-85867.
[15] Paik, J.; Dhillon, S. Drugs. 2018, 78, 1247-1257.
[16] Glomb, T.; Szymankiewicz, K.; wiatek, P. Molecules. 2018, 23, 3361.
[17] Ahsan, M. J. Mini Rev Med Chem. 2022, 22, 164-197.
[18] Kaur, K.; Jaitak, V. Anticancer Agents Med Chem. 2019, 19, 962-983.
[19] Asati, V.; Bhupal, R.; Bhattacharya, S.; Kaur, K.; Gupta, G. D.; Pathak, A.; Mahapatra, D. K. Anticancer Agents Med Chem. 2023, 23, 404-416.
[20] Loscocco, F.; Visani, G.; Galimberti, S.; Curti, A.; Isidori, A. Front Oncol. 2019, 9, 939.
[21] Tantak, M. P.; Kumar, A.; Noel, B.; Shah, K.; Kumar, D. ChemMedChem. 2013, 8, 1468-1474.
[22] Kaur, K.; Jaitak, V. Anticancer Agents Med Chem. 2019, 19, 962-983.
[23] Shu, B.; Yu, Q.; Hu, D.; Che, T.; Zhang, S.; Li, D. Bioorg Med Chem Lett. 2020, 30, 126925.
[24] Sagredou, S.; Dalezis, P.; Nikoleousakos, N.; Nikolaou, M.; Voura, M.; Almpanakis, K.; Panayiotidis, M. I.; Sarli, V.; Trafalis, D. T. Onco Targets Ther. 2020, 13, 7369-7386.
[25] Fu, X.; Huang, J.; Li, N.; Liu, Y.; Liu, Q.; Yuan, S.; Xu, Y.; Chen, Y.; Zhao, Y.; Song, J.; Zhang, S.; Bai, Y. Eur J Med Chem. 2023, 262, 115883.
[26] Puri, S.; Stefan, K.; Khan, S. L.; Pahnke, J.; Stefan, S. M.; Juvale, K. J Med Chem. 2023, 66, 657-676.
[27] Wang, Z.; Cai, J.; Cheng, J.; Yang, W.; Zhu, Y.; Li, H.; Lu, T.; Chen, Y.; Lu, S. J Med Chem. 2021, 64, 2878-2900.
[28] Ju, Z.; Su, M.; Hong, J.; La Kim, E.; Moon, H. R.; Chung, H. Y.; Kim, S.; Jung, J. H. Eur J Med Chem. 2019, 180, 86-98.
[29] Boschelli, D. H.; Connor, D. T.; Bornemeier, D. A.; Dyer, R. D.; Kennedy, J. A.; Kuipers, P. J.; Okonkwo, G. C.; Schrier, D. J.; Wright, C. D. J Med Chem. 1993, 36, 1802-1810.
[30] Ullah, H.; Aslam, M. W.; Rahim, F.; Hussain, A.; Perviaz, M. Chem. Data Collect. 2023, 45, 101031.
[31] Thompson, C. B. Science. 1995, 267, 1456-1462.
[32] Gregory, C. D. Immunol Rev. 2023, 319, 100-127.
[33] Gottlieb, E.; Armour, S. M.; Harris, M. H.; Thompson, C. B. Cell Death Differ. 2003, 10, 709-717.
[34] Begum, H. M.; Shen, K. WIREs Mech Dis. 2023, 15, e1595.
[35] Glorieux, C.; Liu, S.; Trachootham, D.; Huang, P. Nat Rev Drug Discov. 2024, 23, 583-606.
[36] Harris, I. S.; Denicola, G. M. Trends Cell Biol. 2020, 30, 440-451.
[37] Moloney, J. N.; Cotter, T. G. Semin Cell Dev Biol. 2018, 80, 50-64.
[38] Matthews, H. K.; Bertoli, C.; de Bruin, R. A. M. Nat Rev Mol Cell Biol. 2022, 23, 74-88.
[39] Corrales, E.; Levit-Zerdoun, E.; Metzger, P.; Mertes, R.; Lehmann, A.; Münch, J.; Lemke, S.; Kowar, S.; Boerries, M. Cell Commun Signal. 2022, 20, 187.
[40] Irvine, M.; Stewart, A.; Pedersen, B.; Boyd, S.; Kefford, R.; Rizos, H. Oncogenesis. 2018, 7, 72.
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