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

Authors

Tyler A. Johnson
Joseph D. Morris
David A. Coppage
Colon V. Cook
Lauren N. Persi
Marcos A. Ogarrio
Taylor C. Garcia
Nicole L. McIntosh
Erin P. McCauley
Joe Media, Henry Ford HealthFollow
Mani Maheshwari, Henry Ford HealthFollow
Frederick A. Valeriote, Henry Ford HealthFollow
Jiajiu Shaw
Phillip Crews

Recommended Citation

Johnson TA, Morris JD, Coppage DA, Cook CV, Persi LN, Ogarrio MA, Garcia TC, McIntosh NL, McCauley EP, Media J, Maheshwari M, Valeriote FA, Shaw J, and Crews P. Reinvestigation of Mycothiazole Reveals the Penta-2,4-dien-1-ol Residue Imparts Picomolar Potency and 8S Configuration. ACS Med Chem Lett 2020; 11(2):108-113.

Document Type

Article

Publication Date

2-13-2020

Publication Title

ACS Med Chem Lett

Abstract

Reinvestigation of mycothiazole (1) revealed picomolar potency (IC50 = 0.00016, 0.00027, 0.00035 muM) against pancreatic, (PANC-1), liver (HepG2), and colon (HCT-116) tumor cell lines. Reevaluation of 1 provided [alpha]D data indicating Vanuatu specimens of C. mycofijiensis contain the 8S enantiomer of 1 and not the 8R configuration previously reported. Semisynthesis provided 8-O-acetylmycothiazole (2), 8-oxomycothiazole (8), mycothiazole nitrosobenzene derivatives (MND1, MND2: 9a, 9b), and MND3 (10) with IC50 = 0.00129, >1.0, >1.0, >1.0, >1.0 muM, 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 1 required for its cytotoxicty against tumor cell lines.

PubMed ID

32071675

Volume

11

Issue

2

First Page

108

Last Page

113