Reinvestigation of Mycothiazole Reveals the Penta-2,4-dien-1-ol Residue Imparts Picomolar Potency and 8 Configuration.

Reinvestigation of mycothiazole () revealed picomolar potency (IC = 0.00016, 0.00027, 0.00035 μM) against pancreatic, (PANC-1), liver (HepG2), and colon (HCT-116) tumor cell lines. Reevaluation of provided [α] data indicating Vanuatu specimens of contain the 8 enantiomer of and not the 8 configuration previously reported. Semisynthesis provided 8--acetylmycothiazole (), 8-oxomycothiazole (), mycothiazole nitrosobenzene derivatives (MND1, MND2: , ), and MND3 () with IC = 0.00129, >1.0, >1.0, >1.0, >1.0 μM, respectively, against PANC-1 cell lines. These results highlight the significance of the penta-2,4-dien-1-ol residue as a key structural feature of required for its cytotoxicty against tumor cell lines.