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Open AccessArticle

Exploring New Structural Features of the 18β-Glycyrrhetinic Acid Scaffold for the Inhibition of Anaplastic Lymphoma Kinase

1
College of Public Basic Sciences, Jinzhou Medical University, Jinzhou 121001, China
2
School of Chemical and Environmental Engineering, Liaoning University of Technology, Jinzhou 121001, China
3
School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China
4
College of Pharmacy, Jinzhou Medical University, Jinzhou 121001, China
*
Authors to whom correspondence should be addressed.
Molecules 2019, 24(19), 3631; https://doi.org/10.3390/molecules24193631
Received: 20 September 2019 / Revised: 2 October 2019 / Accepted: 3 October 2019 / Published: 8 October 2019
(This article belongs to the Section Medicinal Chemistry)
Novel 18β-glycyrrhetinic acid derivatives possessing a carbamate moiety and structurally similar ester derivatives were developed and evaluated for their efficacy as antitumor inhibitors. In the cellular assays, most of the N-substituted carbamate derivatives at the C3-position exhibited potent activities. The results of SAR investigation revealed that the introduction of the morpholine group at the C30-COOH led to a significant loss of the inhibitory potency. Among the ester derivatives, the ester group at C3-position also determined a noticeable reduction in the efficacy. Compound 3j exhibited the most prominent antiproliferative activity against six human cancer cells (A549, HT29, HepG2, MCF-7, PC-3, and Karpas299). Furthermore, compound 3j exerted a moderate inhibiting effect on the ALK. The results of molecular docking analyses suggested that it could bind well to the active site of the receptor ALK, which was consistent with the biological data. These results might inspire further structural optimization of 18β-glycyrrhetinic acid aiming at the development of potent antitumor agents. The structures 4d, 4g, 4h, 4j, and 4n were studied by X-ray crystallographic analyses. View Full-Text
Keywords: 18β-glycyrrhetinic acid; carbamate moiety; antitumor inhibitors 18β-glycyrrhetinic acid; carbamate moiety; antitumor inhibitors
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MDPI and ACS Style

Cai, D.; Zhang, Z.; Chen, Y.; Zhang, Y.; Sun, Y.; Gong, Y. Exploring New Structural Features of the 18β-Glycyrrhetinic Acid Scaffold for the Inhibition of Anaplastic Lymphoma Kinase. Molecules 2019, 24, 3631.

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