共 126 条
The recent developments of camptothecin and its derivatives as potential anti-tumor agents
被引:69
作者:

Wang, Xianzhang
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Yantai Univ, Sch Pharm, Yantai 264005, Peoples R China Yantai Univ, Sch Pharm, Yantai 264005, Peoples R China

Zhuang, Yumeng
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Yantai Univ, Sch Pharm, Yantai 264005, Peoples R China Yantai Univ, Sch Pharm, Yantai 264005, Peoples R China

Wang, Yuankun
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Yantai Univ, Sch Pharm, Yantai 264005, Peoples R China Yantai Univ, Sch Pharm, Yantai 264005, Peoples R China

Jiang, Maokai
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Yantai Univ, Sch Pharm, Yantai 264005, Peoples R China Yantai Univ, Sch Pharm, Yantai 264005, Peoples R China

Yao, Lei
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Yantai Univ, Sch Pharm, Yantai 264005, Peoples R China Yantai Univ, Sch Pharm, Yantai 264005, Peoples R China
机构:
[1] Yantai Univ, Sch Pharm, Yantai 264005, Peoples R China
关键词:
Camptothecin;
Antitumor;
Derivatives;
Development;
TOPOISOMERASE-I INHIBITORS;
CELLULAR UPTAKE;
CYTOTOXIC ACTIVITY;
MOLECULAR DOCKING;
NATURAL-PRODUCTS;
PRODRUG;
DESIGN;
FL118;
VITRO;
PROLIFERATION;
D O I:
10.1016/j.ejmech.2023.115710
中图分类号:
R914 [药物化学];
学科分类号:
100701 ;
摘要:
This review article focuses on the research progress made in the structural modifications of camptothecin (CPT), a potent cytotoxic natural alkaloid. CPT possesses a unique 5-fused ring structure and exhibits various beneficial activities such as anti-proliferative, anti-fungal, insecticidal, and anti-SARS-CoV-2 properties. CPT and its analogs, including Topotecan and Irinotecan, have been successfully developed and marketed as topoisomerase I inhibitors. To enhance the therapeutic potential of CPT, researchers have undertaken structural modifications primarily on the A, B, and E rings of the CPT core structure. These modifications aim to improve the efficacy, selectivity, and pharmacokinetic properties of CPT derivatives. The article reviews the advancements in hybridizing CPT with other bioactive compounds, the synthesis of novel CPT analogs, and their associated biological activities. Moreover, the structure-activity relationship (SAR) of these modified CPT derivatives is summarized to gain insights into their structure-function correlations. In addition to discussing the modifications and biological activities of CPT derivatives, the article also touches upon the mechanism of parent drug release. Many CPT derivatives are prodrugs, meaning they require metabolic activation to generate the active form of the drug. It is a resource for researchers interested in developing novel anti-tumor agents based on CPT, addressing the limitations associated with the parent drug, and exploring various aspects of CPT modifications.
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Uppalapati, S
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机构: Dr Reddys Labs Ltd, Discovery Res, Hyderabad 500049, Andhra Pradesh, India

Jiwatani, S
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机构: Dr Reddys Labs Ltd, Discovery Res, Hyderabad 500049, Andhra Pradesh, India

Srinivas, NR
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机构: Dr Reddys Labs Ltd, Discovery Res, Hyderabad 500049, Andhra Pradesh, India