Synthesis, characterization, and anti-melanoma activity of tetra-O-substituted analogs of nordihydroguaiaretic acid

Ross O. Meyers; Joshua D. Lambert; Nicole Hajicek; Alan Pourpak; John A. Kalaitzis; Robert T. Dorr

doi:10.1016/j.bmcl.2009.06.063

Synthesis, characterization, and anti-melanoma activity of tetra-O-substituted analogs of nordihydroguaiaretic acid

Ross O. Meyers, Joshua D. Lambert, Nicole Hajicek, Alan Pourpak, John A. Kalaitzis, Robert T. Dorr

Cancer Center

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

21 Scopus citations

Abstract

Synthesis of seven semi-synthetic analogs of NDGA is described. An approach to NDGA derivatization is described in which the ortho-phenolic groups are tethered together by one atom, forming a 5-membered heterocyclic ring. The analogs were evaluated for cytotoxicity in four cancer cell lines and compared to NDGA and tetra-O-methyl-NDGA (M4N) (1a). NDGA bis-cyclic sulfate (2a), NDGA bis-cyclic carbonate (2b), and methylenedioxyphenyl-NDGA (2d) and NDGA tetra acetate (1b) showed anti-cancer activity in vitro. Two compounds, (1b) and (2b), were evaluated for anticancer activity in a mouse xenograft model of human melanoma and showed dose-dependent activity.

Original language	English (US)
Pages (from-to)	4752-4755
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	19
Issue number	16
DOIs	https://doi.org/10.1016/j.bmcl.2009.06.063
State	Published - Aug 15 2009

Keywords

Analogs
Cancer
Melanoma
NDGA
Nordihydroguaiaretic acid

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2009.06.063

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title = "Synthesis, characterization, and anti-melanoma activity of tetra-O-substituted analogs of nordihydroguaiaretic acid",

abstract = "Synthesis of seven semi-synthetic analogs of NDGA is described. An approach to NDGA derivatization is described in which the ortho-phenolic groups are tethered together by one atom, forming a 5-membered heterocyclic ring. The analogs were evaluated for cytotoxicity in four cancer cell lines and compared to NDGA and tetra-O-methyl-NDGA (M4N) (1a). NDGA bis-cyclic sulfate (2a), NDGA bis-cyclic carbonate (2b), and methylenedioxyphenyl-NDGA (2d) and NDGA tetra acetate (1b) showed anti-cancer activity in vitro. Two compounds, (1b) and (2b), were evaluated for anticancer activity in a mouse xenograft model of human melanoma and showed dose-dependent activity.",

keywords = "Analogs, Cancer, Melanoma, NDGA, Nordihydroguaiaretic acid",

author = "Meyers, {Ross O.} and Lambert, {Joshua D.} and Nicole Hajicek and Alan Pourpak and Kalaitzis, {John A.} and Dorr, {Robert T.}",

note = "Funding Information: The authors would like to acknowledge Bhashyam S. Iyengar and William A. Remers for their assistance in the naming and characterization of the compounds described in this Letter. Sponsorship: The study was funded by grant CA017094 from the National Institutes of Health, Bethesda, Maryland, USA. ",

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doi = "10.1016/j.bmcl.2009.06.063",

language = "English (US)",

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T1 - Synthesis, characterization, and anti-melanoma activity of tetra-O-substituted analogs of nordihydroguaiaretic acid

AU - Meyers, Ross O.

AU - Lambert, Joshua D.

AU - Hajicek, Nicole

AU - Pourpak, Alan

AU - Kalaitzis, John A.

AU - Dorr, Robert T.

N1 - Funding Information: The authors would like to acknowledge Bhashyam S. Iyengar and William A. Remers for their assistance in the naming and characterization of the compounds described in this Letter. Sponsorship: The study was funded by grant CA017094 from the National Institutes of Health, Bethesda, Maryland, USA.

PY - 2009/8/15

Y1 - 2009/8/15

N2 - Synthesis of seven semi-synthetic analogs of NDGA is described. An approach to NDGA derivatization is described in which the ortho-phenolic groups are tethered together by one atom, forming a 5-membered heterocyclic ring. The analogs were evaluated for cytotoxicity in four cancer cell lines and compared to NDGA and tetra-O-methyl-NDGA (M4N) (1a). NDGA bis-cyclic sulfate (2a), NDGA bis-cyclic carbonate (2b), and methylenedioxyphenyl-NDGA (2d) and NDGA tetra acetate (1b) showed anti-cancer activity in vitro. Two compounds, (1b) and (2b), were evaluated for anticancer activity in a mouse xenograft model of human melanoma and showed dose-dependent activity.

AB - Synthesis of seven semi-synthetic analogs of NDGA is described. An approach to NDGA derivatization is described in which the ortho-phenolic groups are tethered together by one atom, forming a 5-membered heterocyclic ring. The analogs were evaluated for cytotoxicity in four cancer cell lines and compared to NDGA and tetra-O-methyl-NDGA (M4N) (1a). NDGA bis-cyclic sulfate (2a), NDGA bis-cyclic carbonate (2b), and methylenedioxyphenyl-NDGA (2d) and NDGA tetra acetate (1b) showed anti-cancer activity in vitro. Two compounds, (1b) and (2b), were evaluated for anticancer activity in a mouse xenograft model of human melanoma and showed dose-dependent activity.

KW - Analogs

KW - Cancer

KW - Melanoma

KW - NDGA

KW - Nordihydroguaiaretic acid

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Synthesis, characterization, and anti-melanoma activity of tetra-O-substituted analogs of nordihydroguaiaretic acid

Abstract

Keywords

ASJC Scopus subject areas

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