Synthesis and antitumor activity evaluation of glycoconjugates derived from natural product harmine

LIU Xiaohan; TAN Yunying; LI Qiang; CHEN Xu; FU Junjie; YIN Jian

doi:10.11665/j.issn.1000-5048.2023041101

Journal of China Pharmaceutical University > 2023 > 54(6): 729-742. > DOI: 10.11665/j.issn.1000-5048.2023041101

LIU Xiaohan, TAN Yunying, LI Qiang, CHEN Xu, FU Junjie, YIN Jian. Synthesis and antitumor activity evaluation of glycoconjugates derived from natural product harmine[J]. Journal of China Pharmaceutical University, 2023, 54(6): 729-742. DOI: 10.11665/j.issn.1000-5048.2023041101

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Synthesis and antitumor activity evaluation of glycoconjugates derived from natural product harmine

1.
Key Laboratory of Carbohydrate Chemistry and Biotechnology (Ministry of Education), School of Biotechnology, Jiangnan University, Wuxi 214122
2.
School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China

Funds: This study was supported by the Open Project of Key Laboratory of Carbohydrate Chemistry and Biotechnology (Ministry of Education), Jiangnan University (No.KLCCB-KF202003)

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Received Date: April 10, 2023
Revised Date: December 11, 2023

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Abstract

Abstract

Based on our previous work, the study herein designed and synthesized eight glycoconjugates of natural product harmine (14a-14h)by introducing a cyclohexylmethyloxyl group at its C⁷ position and coupling a methyl-2-amino-β-D-glucopyranoside to the N⁹ position through different lengths of alkyl chains.In vitro anti-tumor activity screening and structure-activity relationship studies showed that the antitumor activity of the conjugates increased with the lengthening of the alkyl chain in the linker.Compound 14h exhibited significantly better proliferative inhibitory activity against MDA-MB-231 breast cancer cells than harmine.As compared to harmine, the introduction of the carbohydrate moiety improved the water solubility of compound 14h and enhanced its tumor cell selectivity through the Warburg effect.Mechanism of action studies revealed that compound 14h induced apoptosis and G0/G1 cell cycle arrest in MDA-MB-231 cells, and inhibited tumor cell migration by interfering with epithelial-mesenchymal transition process.This study provides a new approach for the development of antitumor drugs based on harmine.
- harmine,
- 2-amino-2-deoxy-D-glucose,
- glycoconjugate drugs,
- antitumor activity

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References

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