High-Resolution
MS, MS/MS, and UV Database of Fungal
Secondary Metabolites as a Dereplication Protocol for Bioactive Natural
Products
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Abstract
A major problem in the discovery
of new biologically active compounds
from natural products is the reisolation of known compounds. Such
reisolations waste time and resources, distracting chemists from more
promising leads. To address this problem, dereplication strategies
are needed that enable crude extracts to be screened for the presence
of known compounds before isolation efforts are initiated. In a project
to identify anticancer drug leads from filamentous fungi, a significant
dereplication challenge arises, as the taxonomy of the source materials
is rarely known, and, thus, the literature cannot be probed to identify
likely known compounds. An ultraperformance liquid chromatography–photodiode
array–high-resolution tandem mass spectrometric (UPLC-PDA-HRMS-MS/MS)
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, utilizing both positive-
and negative-ionization modes. Additional details, such as UV-absorption
maxima and retention times, were also recorded. Small-scale cultures
that showed cytotoxic activities were dereplicated before engaging
in the scale-up or purification processes. Using these methods, approximately
50% of the cytotoxic extracts could be eliminated from further study
after the confident identification of known compounds. The specific
attributes of this dereplication methodology include a focus on bioactive
secondary metabolites from fungi, the use of a 10 min chromatographic
method, and the inclusion of both HRMS and MS/MS data