Repurposing Artemisinin-Based Drugs from Antimalarial to Pan-Therapeutic - Pharmacological Promise and Therapeutic Challenges

Sep 23, 2026

Artemisinin (ART) and its derivatives (ARTs) originate from traditional Chinese medicine and were developed as highly effective antimalarial agents. Their cytotoxic activity, driven by a characteristic endoperoxide bridge and subsequent generation of reactive species, supports multiple anticancer mechanisms, including effects on chemoresistant malignancies. ARTs also show therapeutic expansion beyond oncology, covering conditions such as Alzheimer’s disease and reproductive disorders. The review highlights advances in rational design of ART-derived hybrids and nano-enabled delivery systems to improve efficacy and cancer-specific targeting, aiming to guide precision medicine development.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages28

Reading Time1 h 11 min

AccessFree to download

Abstract

Introduction

Artemisinin source and antimalarial origin

Mechanisms of cytotoxicity

Cellular targets and anticancer rationale

Background and clinical context

Article metadata

Drug Design, Development and Therapy Open Access Full Text Article REVIEW Repurposing Artemisinin-Based Drugs from Antimalarial to Pan-Therapeutic: Pharmacological Promise and Therapeutic Challenges Di Wu 1 , *, Hong Zeng 2 , *, Jiachen Tan 1 , Qinzheng Xu 1 , 3 , Faheem Ahmed Khan4 , Nuruliarizki Shinta Pandupuspitasari 5 , Shengqiang Yang2 , Chunjie Huang 1 1School of Medicine, Nantong University, Nantong, 226001, People’s Republic of China; 2School of Basic Medicine, Youjiang Medical University for Nationalities, Baise, 533000, People’s Republic of China; 3Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, Nantong, 226001, People’s Republic of China; 4Research Center for Animal Husbandry, National Research and Innovation Agency, Jakarta Pusat, 10340, Indonesia; 5Faculty of Animal and Agricultural Sciences, Universitas Diponegoro, Semarang, 50275, Indonesia *These authors contributed equally to this work Correspondence: Shengqiang Yang; Chunjie Huang, Email [1243884393@qq.com](1243884393@qq.com); [goodlife.huang@ntu.edu.cn](goodlife.huang@ntu.edu.cn) | Abstract: The sourcing of pharmaceutical agents from natural products remains a cornerstone of drug discovery. For millennia, herbal remedies have served as foundational therapeutic interventions, yet their mechanisms of action often remain elusive. Artemisinin (ART, or “Qinghaosu”) and its derivatives, collectively known as ARTs, exemplify this paradigm. Originating from traditional Chinese medicine, these well-established antimalarial compounds exhibit potent cytotoxicity, positioning them as promising anti-cancer agents. ARTs operate through multiple cancer cell-intrinsic mechanisms and demonstrate synergistic effects with conventional therapies, even against chemoresistant malignancies. Beyond oncology, the therapeutic portfolio of ART-based drugs is rapidly expanding. This review synthesizes recent advancements in the application of ARTs for treating various cancers, Alzheimer’s disease, and reproductive disorders. Furthermore, we explore the frontier of ART drug development, focusing on the rational design of ARTderived molecular hybrids and the engineering of nano-enabled delivery systems. These innovative strategies are pivotal for enhancing anti-cancer efficacy and achieving cancer-specific targeting. Ultimately, this work aims to guide the innovation of ART-based precision medicine, revitalizing the exploration and development of natural products in modern pharmacotherapy.
Keywords: artemisinin, malignancy, neurodegenerative disease, reproductive disorder, drug delivery | | --- | | Introduction
Naturally occurring substances and medicinal plants constitute a significant reservoir of biologically active compounds that are utilized as potent therapeutic modalities across various diseases.1–11 Artemisinin (ART) and its derivatives, collectively known as ARTs, are bioactive sesquiterpene lactones extracted from Artemisia annua, a traditional herbal medicine with antioxidant and anti-inflammatory properties. ART-based combination therapy has been established as the standard treatment for severe malaria, leading to the awarding of the 2015 Nobel Prize in Medicine to the Chinese scientist Tu You-You for her contributions to the isolation and discovery of ART.
Since the 1970s, several ART derivatives, including dihydroartemisinin (DHA) and artesunate (AS), have been identified, exhibiting enhanced solubility and bioavailability 12 (Figure 1) . ARTs have short in vivo half-lives and are capable of diffusing across physiological barriers, such as the blood–brain barrier, which contributes to their advantageous safety and pharmacokinetics in diseases treatment. They contain a tetracyclic core with an endoperoxide bridge (C-O-O-C), which is essential for their cytotoxic properties. Interacting with heme causes the cleavage of the endoperoxide bridge by heme iron (II) oxide, leading to the generation of peroxy free radicals

FAQs

What therapeutic roles do artemisinin-based drugs have beyond malaria?

They are discussed as promising anti-cancer agents and are also described as expanding toward other therapeutic areas including Alzheimer’s disease and reproductive disorders.

How do artemisinin derivatives exert cytotoxic effects at the molecular level?

They contain an endoperoxide bridge that is cleaved by heme iron, generating peroxy free radicals and reactive oxygen species, which damage vulnerable biomolecules and trigger cell death.

Why might ARTs be effective against certain chemoresistant cancers?

The text notes that combining ARTs with conventional chemotherapeutics can improve effectiveness even in cancers exhibiting chemoresistance.

Sep 23, 2026

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