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

doi:10.6023/cjoc202601044

Chinese Journal of Organic Chemistry

ARTICLE

靶向K562肿瘤细胞的1,3,4-噁二唑衍生物的合成、抗癌活性评价及初步作用机制研究

吴越友^a, 何丹丹^a, 冯念林^a, 张依^a, 刘丹丹^a, 周玥^a, 李晨晨^a,*, 王贞超^a,b,*

^a贵州大学药学院,贵州贵阳 550025;
^b绿色农药全国重点实验室,绿色农药与农业生物工程教育部重点实验室,贵州大学精细化工研究开发中心,贵州贵阳 550025

收稿日期:2026-03-24 修回日期:2026-05-26
基金资助:
国家自然科学基金（项目编号：32360689）、贵州省优秀青年学者项目基金（项目编号：GCC[2023]072）、国家重点研发计划（项目编号：2023YFD1400400）以及贵州省基础研究计划（自然科学）青年引导项目（项目编号：QN[2025]010、QN[2025]009）.

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

Wu Yueyou^a, He Dandan^a, Feng Nianlin^a, Zhang Yi^a, Liu Dandan^a, Zhou Yue^a, Li Chenchen^a,*, Wang Zhenchao^a,b,*

^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:2026-03-24 Revised:2026-05-26
Contact: * E-mail: licc@gzu.edu.cn,zcwang@gzu.edu.cn
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).

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, doi: 10.6023/cjoc202601044.

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靶向K562肿瘤细胞的1,3,4-噁二唑衍生物的合成、抗癌活性评价及初步作用机制研究

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

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