Harmine and its derivatives: an In-depth review of antitumor mechanisms and structure-activity relationship

Abstract

Harmine is a naturally occurring heterocyclic compound belonging to the β-carboline alkaloid class, found in various plants, some animals, insects, and marine organisms. Harmine and its derivatives possess significant pharmacological activities, particularly anticancer properties, making them promising candidates for cancer therapy. Despite its efficacy, harmine has adverse effects, including neurotoxicity related to the methoxy group at position 7, which limits its clinical application. To address these limitations, researchers have focused on developing new and more potent derivatives with minimal side effects to improve the therapeutic index and clinical applications of harmine. Therefore, several studies have investigated the anticancer activity of these molecules, revealing their tremendous ability to regulate various cellular mechanisms involved in cell malignancy, including pathways related to cell cycle regulation, apoptosis, and metastasis. This article reviews the most relevant studies conducted in recent years, highlighting the evidence for the anticancer activity of harmine and its derivatives in various cancer cell lines. It also focuses on the mechanisms of action in both in vitro and in vivo models and discusses the structure-activity relationship of the most effective compounds, providing insights into future drug development strategies.