title: In situ imaging and proteome profiling indicate andrographolide is a highly promiscuous compound.
abstract: Natural products represent an enormous source of pharmacologically useful compounds, and are often used as the starting point in modern drug discovery. Many biologically interesting natural products are however not being pursued as potential drug candidates, partly due to a lack of well-defined mechanism-of-action. Traditional in vitro methods for target identification of natural products based on affinity protein enrichment from crude cellular lysates cannot faithfully recapitulate protein-drug interactions in living cells. Reported herein are dual-purpose probes inspired by the natural product andrographolide, capable of both reaction-based, real-time bioimaging and in situ proteome profiling/target identification in live mammalian cells. Our results confirm that andrographolide is a highly promiscuous compound and engaged in covalent interactions with numerous previously unknown cellular targets in cell type-specific manner. We caution its potential therapeutic effects should be further investigated in detail.
authors.affiliation: 1] Department of Chemistry, National University of Singapore, Singapore 117543 [2] Key Laboratory of Flexible Electronics (KLOFE) &Institute of Advanced Materials (IAM), National Jiangsu Synergistic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University (NanjingTech), Nanjing 211816, P. R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Chemistry, National University of Singapore, Singapore 117543.
authors.forename: Hadhi
authors.initials: H
authors.lastname: Wijaya
authors.affiliation: Department of Chemistry, National University of Singapore, Singapore 117543.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Samanta
authors.affiliation: Department of Chemistry, National University of Singapore, Singapore 117543.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Lam
authors.affiliation: Department of Chemistry, National University of Singapore, Singapore 117543.
authors.forename: Shao Q
authors.initials: SQ
authors.lastname: Yao
mesh_terms: D045744:Cell Line, Tumor; D003199:Computer Systems; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D021621:Imaging, Three-Dimensional; D007700:Kinetics; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results
chemical_list: D004224:Diterpenes; D005456:Fluorescent Dyes; D020543:Proteome; C030419:andrographolide