Bridging Bioassay-Guided Isolation and Metabolomics: Toward Hybrid Strategies in Natural Product Drug Discovery

Le résumé fourni par la source

Natural product (NP) remains an important source of drug discovery, providing approximately 32% of newly introduced small molecule drugs between 1981 to 2019. Their unique chemical complexity presents an abundance of active novel chemical entities, but it also raises challenges in its identification and isolation. Two primary methods dominate these fields: the traditional bioassay-guided isolation (BGI) and the more recent metabolomics-based discovery approaches. Despite extensive use of both methods, a systematic framework that integrates their complementary strengths remain insufficiently developed. To address this gap, this review proposes an integrative framework that links metabolomics-based compound prioritization with subsequent BGI validation. This review critically evaluates findings from peer-reviewed studies published between 1958 to 2024 to compare the principles, technical capabilities, strengths limitations, and bridges their integrative applications in NP drug discovery. Our analysis shows that metabolomics excels in early-stage exploration by providing broad chemical coverage, high sensitivity, and efficient prioritization of active novel compounds, while BGI remains essential for definitive isolation, mechanistic evaluation, and biological activity confirmation. By framing metabolomics as a decision-support stage rather than a replacement for BGI workflows, this review emphasizes integrative discovery that improves efficiency, reduce rediscovery, and preserve chemical rigor. Such hybrid strategies could reduce the research timeline for the discovery of NP-based new chemical entity with improved precision and reproducibility.

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