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.",

keywords = "Mycothiazole, Cytotoxic, Picomolar",

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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