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

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

doi:10.1021/acsmedchemlett.9b00302

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

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

Department of Natural Sciences and Mathematics

Research output: Contribution to journal › Letter › peer-review

Abstract

Reinvestigation of mycothiazole (1) revealed picomolar potency (IC(50) = 0.00016, 0.00027, 0.00035 μM) against pancreatic, (PANC-1), liver (HepG2), and colon (HCT-116) tumor cell lines. Reevaluation of 1 provided [α](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 IC(50) = 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 1 required for its cytotoxicty against tumor cell lines.

Original language	American English
Pages (from-to)	108-113
Number of pages	6
Journal	ACS Medicinal Chemistry Letters
Volume	11
Issue number	2
DOIs	https://doi.org/10.1021/acsmedchemlett.9b00302
State	Published - Jan 2 2020

Keywords

Mycothiazole
Cytotoxic
Picomolar

Disciplines

Medicinal Chemistry and Pharmaceutics

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Johnson, T. A., Morris, J. D., Coppage, D., Cook, C. V., Persi, L., Ogarrio, M. A., Garcia, T. C., McIntosh, N. L., McCauley, E. P., Media, J., Maheshwari, M., Valeriote, F. A., Shaw, J., & Crews, P. (2020). Reinvestigation of Mycothiazole Reveals the Penta-2,4-dien-1-ol Residue Imparts Picomolar Potency and 8S Configuration. ACS Medicinal Chemistry Letters, 11(2), 108-113. https://doi.org/10.1021/acsmedchemlett.9b00302

Johnson, TA, Morris, JD, Coppage, D, Cook, CV, Persi, L, Ogarrio, MA, Garcia, TC, McIntosh, NL, McCauley, EP, Media, J, Maheshwari, M, Valeriote, FA, Shaw, J & Crews, P 2020, 'Reinvestigation of Mycothiazole Reveals the Penta-2,4-dien-1-ol Residue Imparts Picomolar Potency and 8S Configuration', ACS Medicinal Chemistry Letters, vol. 11, no. 2, pp. 108-113. https://doi.org/10.1021/acsmedchemlett.9b00302

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

abstract = "Reinvestigation of mycothiazole (1) revealed picomolar potency (IC(50) = 0.00016, 0.00027, 0.00035 μM) against pancreatic, (PANC-1), liver (HepG2), and colon (HCT-116) tumor cell lines. Reevaluation of 1 provided [α](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 IC(50) = 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 1 required for its cytotoxicty against tumor cell lines.",

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author = "Johnson, \{Tyler A.\} and Morris, \{Joseph D.\} and David Coppage and Cook, \{Colon V.\} and Lauren Persi and Ogarrio, \{Marcos A.\} and Garcia, \{Taylor C.\} and McIntosh, \{Nicole L.\} and McCauley, \{Erin P.\} and Joseph Media and Mani Maheshwari and Valeriote, \{Frederick A.\} and Jiajiu Shaw and Phillip Crews",

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doi = "10.1021/acsmedchemlett.9b00302",

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AU - Johnson, Tyler A.

AU - Morris, Joseph D.

AU - Coppage, David

AU - Cook, Colon V.

AU - Persi, Lauren

AU - Ogarrio, Marcos A.

AU - Garcia, Taylor C.

AU - McIntosh, Nicole L.

AU - McCauley, Erin P.

AU - Media, Joseph

AU - Maheshwari, Mani

AU - Valeriote, Frederick A.

AU - Shaw, Jiajiu

AU - Crews, Phillip

PY - 2020/1/2

Y1 - 2020/1/2

N2 - Reinvestigation of mycothiazole (1) revealed picomolar potency (IC(50) = 0.00016, 0.00027, 0.00035 μM) against pancreatic, (PANC-1), liver (HepG2), and colon (HCT-116) tumor cell lines. Reevaluation of 1 provided [α](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 IC(50) = 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 1 required for its cytotoxicty against tumor cell lines.

AB - Reinvestigation of mycothiazole (1) revealed picomolar potency (IC(50) = 0.00016, 0.00027, 0.00035 μM) against pancreatic, (PANC-1), liver (HepG2), and colon (HCT-116) tumor cell lines. Reevaluation of 1 provided [α](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 IC(50) = 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 1 required for its cytotoxicty against tumor cell lines.

KW - Mycothiazole

KW - Cytotoxic

KW - Picomolar

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