Clinical development and informatics analysis of natural and semi-synthetic flavonoid drugs: A critical review

Kuo Xu; Xia Ren; Jintao Wang; Qin Zhang; Xianjun Fu; Pei-Cheng Zhang

doi:10.1016/j.jare.2023.11.007

Clinical development and informatics analysis of natural and semi-synthetic flavonoid drugs: A critical review

J Adv Res. 2023 Nov 8:S2090-1232(23)00330-2. doi: 10.1016/j.jare.2023.11.007. Online ahead of print.

Authors

Kuo Xu¹, Xia Ren¹, Jintao Wang², Qin Zhang², Xianjun Fu³, Pei-Cheng Zhang⁴

Affiliations

¹ Research Institute for Marine Traditional Chinese Medicine, Key Laboratory of Marine Traditional Chinese Medicine in Shandong Universities, Shandong Engineering and Technology Research Center on Omics of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China; Qingdao Academy of Chinese Medical Sciences Shandong University of Traditional Chinese Medicine, Qingdao Key Laboratory of Research in Marine Traditional Chinese Medicine, Qingdao Key Technology Innovation Center of Marine Traditional Chinese Medicine's Deep Development and Industrialization, Qingdao 266114, China.
² Chongqing Kangzhou Big Data (Group) Co., Ltd., Chongqing 401336, China.
³ Research Institute for Marine Traditional Chinese Medicine, Key Laboratory of Marine Traditional Chinese Medicine in Shandong Universities, Shandong Engineering and Technology Research Center on Omics of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China; Qingdao Academy of Chinese Medical Sciences Shandong University of Traditional Chinese Medicine, Qingdao Key Laboratory of Research in Marine Traditional Chinese Medicine, Qingdao Key Technology Innovation Center of Marine Traditional Chinese Medicine's Deep Development and Industrialization, Qingdao 266114, China. Electronic address: fuxianjun@sdutcm.edu.cn.
⁴ State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China. Electronic address: pczhang@imm.ac.cn.

PMID: 37949300
DOI: 10.1016/j.jare.2023.11.007

Abstract

Background: Flavonoids are one of the most important metabolites with vast structural diversity and a plethora of potential pharmacological applications, which have drawn considerable attention in the laboratory. Nevertheless, it remains uncertain how many candidates were progressed to clinical application.

Aim of review: We carried out a critical review of natural and semi-synthetic flavonoid drugs and candidates undergoing different clinical phases worldwide by applying an adequate search method and conducted a brief cheminformatic and bioinformatic analysis. It was expected that the obtained results might narrow the screening scope and reduce the cost of drug research and development.

Key scientific concepts of review: To our knowledge, this is the most systematic summarization of flavonoid-based drugs and clinical candidates to date. It was found that a total of 19 flavonoid-based drugs have been approved for the market, and of these, natural flavonoids accounted for 52.6%. Besides, a total of 36 flavonoid-based clinical candidates are undergoing or suspended in different phases, and of these, natural flavonoids account for 44.4%. Thus, natural flavonoids remain the best option for finding novel agents/active templates, and when investigated in conjunction with synthetic chemicals and biologicals, they offer the potential to discover novel structures that can lead to effective agents against a variety of human diseases. Additionally, flavonoid-based marketed drugs have been successful in cardiovascular treatment, and the related drugs account for more than 30% of marketed drugs. However, the use of flavonoids as antineoplastic and immunomodulating agents is not likely for approximately 50% of the candidates suspended in the clinical stage. Interestingly, the marketed drugs covered a broader range of chemical spaces based on size, polarity, and three-dimensional structure compared to the clinical candidates. In addition, flavonoid glycosides with poor oral bioavailability account for 36.8% of the marketed drugs, and thus, they could be thoroughly investigated.

Keywords: Chemometrics; Flavan; Flavone; Flavonol; Semi-synthetic flavonoid.

Publication types

Review