Marine Natural Product Libraries for High-Throughput Screening and Rapid Drug Discovery

Abstract

There is a need for diverse molecular libraries for phenotype-selective and high-throughput screening. To make marine natural products (MNPs) more amenable to newer screening paradigms and shorten discovery time lines, we have created an MNP library characterized online using MS. To test the potential of the library, we screened a subset of the library in a phenotype-selective screen to identify compounds that inhibited the growth of BRCA2-deficient cells.

Spirotoamides A and B, novel 6,6-spiroacetal polyketides isolated from a microbial metabolite fraction library

“…The overall structure was constructed using long-range correlations in the HMBC spectrum (Supplementary Figure S6). The HMBC correlations from H-2 and H-3 to C-1 permitted the assignment of the carbonyl carbon as C-1 and the amide group was established by the 13 C chemical shift and molecular formula. The ethyl branch at C-4 and the connectivities from C-3 to Spirotoamides A and B from a fraction library T Nogawa et al C-5 were confirmed by the HMBC correlations from H-2¢ to C-4, from H-1¢ to C-3 and C-5, from H-2 to C-4 and from H-5 to C-3.…”

“…14-Me, H-14 and H-16 showed HMBC correlations to C-15, establishing the connectivities from C-14 to C-16 through the acetal carbon C-15. A 6,6-spiro-ring system was constructed in consideration of the 13 C chemical shift value of C-15 at 101.9 p.p.m. [14][15][16][17][18][19] and the hydrogen deficiency index of 5, which was also confirmed by the correlations between H-12 and 14-Me, between H-17 and H-19 and between 14-Me and H-16eq in the ROESY spectrum (Supplementary Figure S7).…”

“…IR spectra were recorded on a HORIBA FT-720 with a DuraSampl IR II ATR instrument (HORIBA). NMR data were obtained at 500 MHz for 1 H NMR and 125 MHz for 13 C NMR on a JEOL ECP-500 or ECA-500 spectrometer (JEOL, Tokyo, Japan …”

“…We discovered and isolated verticilactam 6 from S. spiroveticillatus JC-8444, a tautomycin producer, [7][8][9] and the new fraquinocins I and J 10 and 6-dimethylalylindole-3-carbaldehyde 11 from S. reveromyceticus SN-593, a reveromycin producer 12 by our methodology constructing the fraction library. Also, Bugni et al 13 reported a marine natural products library by HPLC-MS fractionation for rapid drug discovery. These reports have demonstrated the advantage of fraction libraries in isolating and investigating the activities of natural products.…”

Bioprospecting: Creating a Value for Biodiversity

“…Various technical problems undoubtedly exist with the screening and isolation of natural products, but the rewards for overcoming them would seem to justify the effort required, and technical solutions are being described in the literature. For example, purification and identification of natural products are believed to be difficult and slow: high throughput separation methods coupled with sensitive analytical techniques can resolve this (Bugni et al, 2008;Hu et al, 2008). Natural products are chemically complex: comparisons of the chemical properties of collections of natural products show that they more closely match the "chemical space" of successful drugs than collections of synthetic chemicals (Grabowski and Schneider 2007;Ganesan 2008).…”