Deguelin’s Anticancer Bioactivity: Challenges and Opportunities in Medicinal Chemistry

Deguelin is a natural isoflavone derived from the rotenone family, commonly found in plants belonging to the Derris and Grifola genera. Comprehensive research has underscored its considerable promise in oncological treatment. Deguelin demonstrates anticancer activity by suppressing cell proliferatio...

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Main Authors: Wenjie Jiang, Jing Zeng, Li Guo, Jianyou Shi, Yang Lei
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1571452/full
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author Wenjie Jiang
Jing Zeng
Li Guo
Jianyou Shi
Yang Lei
author_facet Wenjie Jiang
Jing Zeng
Li Guo
Jianyou Shi
Yang Lei
author_sort Wenjie Jiang
collection DOAJ
description Deguelin is a natural isoflavone derived from the rotenone family, commonly found in plants belonging to the Derris and Grifola genera. Comprehensive research has underscored its considerable promise in oncological treatment. Deguelin demonstrates anticancer activity by suppressing cell proliferation and promoting apoptosis via the modulation of critical signaling pathways, such as NF-κB, Wnt, and AMPK pathways. Moreover, deguelin demonstrates several biological activities, including cell cycle arrest, autophagy modulation, anti-angiogenic and anti-metastatic capabilities, along with antioxidant and anti-inflammatory actions. Notwithstanding these encouraging benefits, the practical utilization of deguelin has been impeded by its volatility, possible neurotoxicity, and other detrimental consequences. This review initially examines the antitumor biological actions of deguelin, incorporating recent discoveries regarding its methods of action. It subsequently consolidates studies on structural alterations intended to enhance the efficacy of deguelin while mitigating its toxicity, and offers a summary of the structure-activity connections of its derivatives. The review seeks to further research on deguelin and guide the development of more efficacious derivatives for prospective clinical applications. This study seeks to establish a robust basis for the advancement of deguelin as a potential chemopreventive agent for cancer.
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spelling doaj-art-a20a151f5786452ea0c6f00208016b2a2025-08-20T03:30:20ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-06-011610.3389/fphar.2025.15714521571452Deguelin’s Anticancer Bioactivity: Challenges and Opportunities in Medicinal ChemistryWenjie Jiang0Jing Zeng1Li Guo2Jianyou Shi3Yang Lei4Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, ChinaSchool of Food and Bioengineering, Xihua University, Chengdu, Sichuan, ChinaThe State Key Laboratory of Southwestern Chinese Medicine Resources, Department of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, ChinaDepartment of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, ChinaDepartment of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, ChinaDeguelin is a natural isoflavone derived from the rotenone family, commonly found in plants belonging to the Derris and Grifola genera. Comprehensive research has underscored its considerable promise in oncological treatment. Deguelin demonstrates anticancer activity by suppressing cell proliferation and promoting apoptosis via the modulation of critical signaling pathways, such as NF-κB, Wnt, and AMPK pathways. Moreover, deguelin demonstrates several biological activities, including cell cycle arrest, autophagy modulation, anti-angiogenic and anti-metastatic capabilities, along with antioxidant and anti-inflammatory actions. Notwithstanding these encouraging benefits, the practical utilization of deguelin has been impeded by its volatility, possible neurotoxicity, and other detrimental consequences. This review initially examines the antitumor biological actions of deguelin, incorporating recent discoveries regarding its methods of action. It subsequently consolidates studies on structural alterations intended to enhance the efficacy of deguelin while mitigating its toxicity, and offers a summary of the structure-activity connections of its derivatives. The review seeks to further research on deguelin and guide the development of more efficacious derivatives for prospective clinical applications. This study seeks to establish a robust basis for the advancement of deguelin as a potential chemopreventive agent for cancer.https://www.frontiersin.org/articles/10.3389/fphar.2025.1571452/fulldeguelindeguelin derivativescancerheat-shock proteinsstructure-activity relationshipHSP90 inhibitor
spellingShingle Wenjie Jiang
Jing Zeng
Li Guo
Jianyou Shi
Yang Lei
Deguelin’s Anticancer Bioactivity: Challenges and Opportunities in Medicinal Chemistry
Frontiers in Pharmacology
deguelin
deguelin derivatives
cancer
heat-shock proteins
structure-activity relationship
HSP90 inhibitor
title Deguelin’s Anticancer Bioactivity: Challenges and Opportunities in Medicinal Chemistry
title_full Deguelin’s Anticancer Bioactivity: Challenges and Opportunities in Medicinal Chemistry
title_fullStr Deguelin’s Anticancer Bioactivity: Challenges and Opportunities in Medicinal Chemistry
title_full_unstemmed Deguelin’s Anticancer Bioactivity: Challenges and Opportunities in Medicinal Chemistry
title_short Deguelin’s Anticancer Bioactivity: Challenges and Opportunities in Medicinal Chemistry
title_sort deguelin s anticancer bioactivity challenges and opportunities in medicinal chemistry
topic deguelin
deguelin derivatives
cancer
heat-shock proteins
structure-activity relationship
HSP90 inhibitor
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1571452/full
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