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

Novel derivatives of nordihydoguaiaretic acid were synthesized and tested for in vitro and in vivo anticancer activity. 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...

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Bibliographic Details
Published in:	Bioorganic & medicinal chemistry letters Vol. 19; no. 16; pp. 4752 - 4755
Main Authors:	Meyers, Ross O., Lambert, Joshua D., Hajicek, Nicole, Pourpak, Alan, Kalaitzis, John A., Dorr, Robert T.
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier Ltd 15-08-2009 Elsevier
Subjects:	Analogs Animals Antineoplastic agents Antineoplastic Agents - chemical synthesis Antineoplastic Agents - therapeutic use Antineoplastic Agents - toxicity Biological and medical sciences Cancer Cell Line, Tumor Dose-Response Relationship, Drug Drug Screening Assays, Antitumor General aspects Humans Masoprocol - analogs & derivatives Masoprocol - chemical synthesis Masoprocol - toxicity Medical sciences Melanoma Melanoma - drug therapy Mice NDGA Nordihydroguaiaretic acid Pharmacology. Drug treatments Xenograft Model Antitumor Assays Analogs NDGA Nordihydroguaiaretic acid Melanoma Cancer Antineoplastic agent Liver Cytotoxicity MTT assay Hepatocyte Malignant melanoma Organic sulfate Masoprocol Colon Mammary gland Chemical synthesis Acylate Tumor cell Human Organic carbonate Malignant tumor In vitro Biological activity Cell line Phenols
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Summary:	Novel derivatives of nordihydoguaiaretic acid were synthesized and tested for in vitro and in vivo anticancer activity. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2009.06.063