Dataset Information

Discovery of Ureido-Based Apcin Analogues as Cdc20-specific Inhibitors against Cancer.

ABSTRACT: Cdc20 is a promising drug target that plays an important role in the mid-anaphase process of cellular mitosis, and Apcin is the only reported core structure of the Cdc20-specific inhibitor. Some potent Apcin derivatives were obtained in our previous research, and a structure-activity relationship was determined. In this study, we designed and synthesized a series of ureido-based Apcin derivatives. The proliferation-inhibition experiments on four cancer-cell lines showed that ureido skeleton could promote the anti-proliferation activity of purine-substituted compounds, whereas the ureido analogues with pyrimidine substitutes showed no significant improvement in the inhibitory effect compared with the original ones. Further tests confirmed that ureido-based compounds can enhance the binding affinity to Cdc20 by increasing the levels of Cdc20 downstream proteins. Compound 27 revealed a remarkably antitumor activity pattern against Hela (IC₅₀ = 0.06 ± 0.02 μM) and potent binding affinity to Cdc20. Moreover, compound 20 induced caspase-dependent apoptosis and cell-cycle arrest at the G2/M phase, and compound 27 induced caspase-dependent apoptosis and promoted microtubule polymerization. Finally, a molecular-docking simulation was performed for compounds 20 and 27 to predict the potential ligand-protein interactions with the active sites of the Cdc20 proteins.

SUBMITTER: He Y

PROVIDER: S-EPMC9964651 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Discovery of Ureido-Based Apcin Analogues as Cdc20-specific Inhibitors against Cancer.

He Yiqin Y Le Xiangyang X Hu Gaoyun G Li Qianbin Q Chen Zhuo Z

Pharmaceuticals (Basel, Switzerland) 20230215 2

Cdc20 is a promising drug target that plays an important role in the mid-anaphase process of cellular mitosis, and Apcin is the only reported core structure of the Cdc20-specific inhibitor. Some potent Apcin derivatives were obtained in our previous research, and a structure-activity relationship was determined. In this study, we designed and synthesized a series of ureido-based Apcin derivatives. The proliferation-inhibition experiments on four cancer-cell lines showed that ureido skeleton coul ...[more]

PMID: 37259447

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Dataset Information

Discovery of Ureido-Based Apcin Analogues as Cdc20-specific Inhibitors against Cancer.

Publications

Discovery of Ureido-Based Apcin Analogues as Cdc20-specific Inhibitors against Cancer.

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