Harnessing Natural Product Diversity for Fluorophore Discovery: Naturally Occurring Fluorescent Hydroxyanthraquinones from the Marine Crinoid Pterometra venusta

Abstract

Fluorescent small molecules are important tools in many aspects of modern biology. A two-stage evaluation process involving fluorescence screening and live-cell imaging was developed to facilitate the identification of new fluorescent probes from extracts housed within the NCI Natural Products Repository. To this end, over 2000 extracts and prefractionated samples were examined, including an extract from the marine crinoid Pterometra venusta. An optically guided evaluation involving stepwise fluorescence screening and live-cell imaging was developed to enable the isolation of fluorescent natural products. These efforts resulted in the isolation of six hydroxyanthraquinone compounds, three of which are new natural products. These purified metabolites were examined for their potential as cellular imaging probes, and they demonstrate that natural product libraries can be a good source of new fluorescent agents.

Anthraquinones, Diphenyl Ethers, and Their Derivatives from the Culture of the Marine Sponge-Associated Fungus Neosartorya spinosa KUFA 1047

“…Based on the biogenetic consideration, the absolute configuration of C-2′ in 4 should be the same as that of C-2′ in 2 , i.e., ( S ). Additionally, this hypothesis was supported by the same sign of their optical rotations (dextrorotatory), which is based on the report by Singh et al [ 17 ], that 1,3,8-trihydroxy-6-(2′-acetoxyptopyl) anthracene-9,10-dione, isolated from the marine crinoid Pterometra venusta , ([α] 25 D + 40, c 0.05, MeOH) and its deacetylated product ([α] 25 D + 37, c 0.05, MeOH) were both dextrorotatory. Literature search revealed that 4 has never been previously reported.…”

Structure and Absolute Configuration of Phenanthro-perylene Quinone Pigments from the Deep-Sea Crinoid Hypalocrinus naresianus

“…Acetylated quinones are not common among natural products, especially among echinoderms. However, acetylated anthraquinones have recently been isolated from the crinoid Pterometra venusta [ 14 ]. Gymnochrome G ( 1 ) and H ( 2 ) represent the first acetylated phenanthroperylene quinone pigments.…”

Creating and screening natural product libraries

“…Interestingly, the prevalence of uorescent molecules in natural product extracts has also provided an opportunity for development of new chemical probes with novel uorophores. 103 Another potential challenge posed in cell-based HTS is the presence of non-specic cytotoxic compounds. Although it is difficult to nd solid corroboration, anecdotally there tends to be an expectation that cytotoxic extracts may be chemically and biologically more diverse than innocuous extracts.…”

“…The development of lead molecules from screening hits derived from natural products is aided by the analysis of structural analogs and establishment of SAR for active compounds oen produced in the same source organism. 99,103,109 Analog development for isolated natural products can also oen be addressed by the development of synthetic methods. 52,100,101 Rocaglamide, from Aglaia extracts, was found to be able to sensitize TRAIL-resistant cells to TRAILinduced apoptosis.…”