De-inventing the wheel: Dereplication tools for natural products research

In ongoing studies to explore filamentous fungi for anticancer drug leads, over 140 compounds have been isolated and characterized over the past four years, with approximately 25 to 35 compounds being discovered annually. Approximately 30% of these represent new chemical entities. To expedite the discovery of new leads, and to avoid re-isolation of previously known compounds, a UPLC-PDA-HRMS method was developed for dereplication of fungal secondary metabolites in crude culture extracts. A database was constructed by recording HRMS and MS/MS spectra of fungal metabolites isolated to date, utilizing both positive and negative ionization modes. Additional information, such as UV-absorption maxima and retention times, were also recorded. Screener cultures that showed cytotoxic activities were dereplicated before engaging in the isolation/purification process. Examples will be presented that demonstrate the speed and efficiencies with these procedures, particularly in conjunction with software programs that help collate the data. Utilizing this work flow, a promising sample can be dereplicated in 45min.