Palladium-Catalyzed Late-Stage Functionalization of Natural Antitumor Drug: Synthesis and Bioactivity of 5-Aryl Camptothecins

IF 3.3 2区生物学 Q2 CHEMISTRY, MEDICINAL

Journal of Natural Products Pub Date : 2025-03-07 DOI:10.1021/acs.jnatprod.4c0134410.1021/acs.jnatprod.4c01344

Lian Sun, Xiao-Long Li, Qiu-Shan Huang, Wan-Sheng Ji, Xiaohuan Li, Jin-Bu Xu* and Feng Gao*,

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引用次数: 0

Abstract

Camptothecin (CPT) and its derivatives have garnered significant interest due to their potent anticancer activity. In this study, 62 novel CPT derivatives (1a–31a and 1b–31b) were designed and synthesized through Pd-catalyzed late-stage modification at the C-5 position. The anticancer efficacy of these compounds against three human cancer cell lines was evaluated. Compounds 5R-12a (IC₅₀ = 0.05 ± 0.01 μM against HCT-116) and 5R-6a (IC₅₀ = 0.04 ± 0.03 μM against MCF-7) exhibited enhanced antitumor activity when compared to CPT. The preliminary mechanism of apoptosis was investigated through cell viability assays, protein expression, and docking analysis. The results indicated that compounds 12a and 6a exhibited a greater ability to induce apoptosis and G2/M phase arrest than did CPT. Docking results provided a possible explanation for the superior activity of the 5R configuration. This work would offer new insights for CPT lead compound development.

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来源期刊

Journal of Natural Products 生物-药学

CiteScore

9.10

自引率

5.90%

发文量

294

审稿时长

2.3 months

期刊介绍： The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin. When new compounds are reported, manuscripts describing their biological activity are much preferred. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.