Comparing the Metabolome of a Caribbean Sponge to 420 FDA Approved Drugs, a Molecular Networking Approach

Abstract

Historically, isolated natural products have provided an unparalleled starting point for drug discovery efforts. However, the dereplication and isolation of promising compounds remains difficult and time-consuming, especially when working with crude extracts. There is a need to create more expeditious strategies to determine the identity and potential activity of compounds early in the process. Molecular networking is a technique developed at UCSD that permits a visual comparison of different small molecules based upon the similarities of their MS/MS fragmentation patterns. One promising application of this technology is to guide the isolation and identification of compounds within extracts based upon their similarity to known compounds. Here we report the use of molecular networking to compare the most abundant metabolites of a sponge extract with 420 FDA approved compounds with known structures and activities. Unknown molecules showing similarities to known drugs were selected for structural elucidation by NMR and biochemical and in-silico assays.