Li, X.; Xun, T.; Xu, H.; Pang, X.; Yang, B.; Wang, J.; Zhou, X.; Lin, X.; Tan, S.; Liu, Y.; Liao, S. Design, Synthesis, and Anticancer Activity of Novel 3,6-Diunsaturated 2,5-Diketopiperazines. Mar. Drugs2023, 21, 325.
Li, X.; Xun, T.; Xu, H.; Pang, X.; Yang, B.; Wang, J.; Zhou, X.; Lin, X.; Tan, S.; Liu, Y.; Liao, S. Design, Synthesis, and Anticancer Activity of Novel 3,6-Diunsaturated 2,5-Diketopiperazines. Mar. Drugs 2023, 21, 325.
Li, X.; Xun, T.; Xu, H.; Pang, X.; Yang, B.; Wang, J.; Zhou, X.; Lin, X.; Tan, S.; Liu, Y.; Liao, S. Design, Synthesis, and Anticancer Activity of Novel 3,6-Diunsaturated 2,5-Diketopiperazines. Mar. Drugs2023, 21, 325.
Li, X.; Xun, T.; Xu, H.; Pang, X.; Yang, B.; Wang, J.; Zhou, X.; Lin, X.; Tan, S.; Liu, Y.; Liao, S. Design, Synthesis, and Anticancer Activity of Novel 3,6-Diunsaturated 2,5-Diketopiperazines. Mar. Drugs 2023, 21, 325.
Abstract
Based on the marine natural products piperafizine B, X334 and our previously reported compound 4m, fourteen novel 3,6-diunsaturated 2,5-diketopiperazine (2,5-DPK) derivatives (1-2, 4-6, 8-16), together with two known ones (3 and 7), were designed and synthesized as anticancer agents against cell lines A549 and Hela. The MTT assay results showed that the derivatives 6, 8-12 and 15 had moderate to good anticancer capacities with the IC50 values ranging from 0.7 to 8.9 μM. Among them, compound 11 with naphthalen-1-ylmethylene and 2-methoxybenzylidene functions at the 3- and 6-positions of 2,5-DPK ring, respectively, displayed good inhibitory activities to both cancer cells A549 (IC50 = 1.2 μM) and Hela (IC50 = 0.7 μM). It could also induce apoptosis and obviously block the cell cycle progression at G2/M phase in both cells at 1.0 μM. The electron withdrawing functions might not be favorable for the derivatives with high anticancer activities. Additionally, compared to piperafizine B and X334, these semi-N-alkylated derivatives have high liposolubilities (> 1.0 mg•mL-1). Compound 11 can be further developed aiming to the discovery of novel anticancer candidate.
Keywords
2,5-diketopiperazine derivative; intermolecular bond; liposolubility; electron property; anticancer
Subject
Medicine and Pharmacology, Medicine and Pharmacology
Copyright:
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