Novel Harmine Derivatives for Tumor Targeted Therapy

Overview

Journal Oncotarget

Specialty Oncology

Date 2015 May 6

PMID 25940702

Citations 11

Authors

Siwen Li

Aqin Wang

Fan Gu

Zhaohui Wang

Caiping Tian

Zhiyu Qian

Liping Tang

Yueqing Gu

Affiliations

Soon will be listed here.

Abstract

Harmine is a beta-carboline alkaloid found in medicinal plant PeganumHarmala, which has served as a folk anticancer medicine. However, clinical applications of harmine were limited by its low pharmacological effects and noticeable neurotoxicity. In this study, we modified harmine to increase the therapeutic efficacy and to decrease the systemic toxicity. Specifically, two tumor targeting harmine derivatives 2DG-Har-01 and MET-Har-02 were synthesized by modifying substituent in position-2, -7 and -9 of harmine ring with two different targeting group2-amino-2-deoxy-D-glucose (2DG) and Methionine (Met), respectively. Their therapeutic efficacy and toxicity were investigated both in vitro and in vivo. Results suggested that the two new harmine derivatives displayed much higher therapeutic effects than non-modified harmine. In particular, MET-Har-02 was more potent than 2DG-Har-01 with promising potential for targeted cancer therapy.

Citing Articles

Anti-tumor potential of Harmine and its derivatives: recent trends and advancements.

Joshi H, Bhushan S, Dimri T, Sharma D, Sak K, Chauhan A Discov Oncol. 2025; 16(1):189.

PMID: 39954215 PMC: 11829886. DOI: 10.1007/s12672-025-01893-w.

Harmine Hydrochloride Induces G2/M Cell Cycle Arrest and Apoptosis in SK-Hep1 Hepatocellular Carcinoma Cells by Regulating Mitogen-Activated Protein Kinases and the PI3K/AKT Pathway.

Kim G Prev Nutr Food Sci. 2024; 28(4):436-443.

PMID: 38188092 PMC: 10764232. DOI: 10.3746/pnf.2023.28.4.436.

In vitro and in vivo Efficacies of Novel Harmine Derivatives in the Treatment of Cystic Echinococcosis.

Chen B, Yan M, Gao H, Ma Q, Li L, Lu G Drug Des Devel Ther. 2023; 17:2441-2454.

PMID: 37637266 PMC: 10454840. DOI: 10.2147/DDDT.S419002.

Harmine reinforces the effects of regorafenib on suppressing cell proliferation and inducing apoptosis in liver cancer cells.

Chen Z, Li J, Zhu S, Li Z, Yu J, Wu J Exp Ther Med. 2022; 23(3):209.

PMID: 35126712 PMC: 8796640. DOI: 10.3892/etm.2022.11132.

Anthranilamides with quinoline and β-carboline scaffolds: design, synthesis, and biological activity.

Beus M, Persoons L, Daelemans D, Schols D, Savijoki K, Varmanen P Mol Divers. 2022; 26(5):2595-2612.

PMID: 34997441 PMC: 8741576. DOI: 10.1007/s11030-021-10347-8.

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