Aleutianamine B, A Novel Chiral Sulfoxide Isolated from Latrunculia spp. and Generated via Semi-Synthesis, Exhibits Selectivity for Ovarian Cancer Cells

We report a new optically active sulfoxide containing
natural product
isolated from an Alaskan Latrunculia spp. collection off the shores of the Aleutian Islands which we
term aleutianamine B. It was identified and characterized in part
via contemporary computational tools. Global Natural Products Social
Molecular Networking (GNPS) analysis was a key tool used in identifying
aleutianamine B in the crude extract. The relative configuration of
the unique stereogenic sulfur atom was determined by DFT computational
analysis. We also report the synthesis of aleutianamine B from aleutianamine.
Aleutianamine B was evaluated against ovarian cancer and normal cell
lines. This revealed that aleutianamine B retained submicromolar potency
against A2780 cells while being ≥50-fold less potent on noncancerous
cells; this was in stark contrast to the parent compound, aleutianamine,
which displayed potent cytotoxicity against normal cell lines. Overall,
the pyrroloiminoquinone (PIQ) class increasingly reveals unique selectivity
and potency for tumor cell groups that are currently resistant to
available chemotherapy, providing significant leads for therapeutics
and biochemical probes.