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.

• Authors: Ross O Meyers, Joshua D Lambert, Nicole Hajicek, Alan Pourpak, John A Kalaitzis, Robert T Dorr
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 19 Issue 16 Pg. 4752-5 (Aug 15 2009) ISSN: 1464-3405 [Electronic] England
• PMID: 19615898 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antineoplastic Agents
• Masoprocol

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, therapeutic use, toxicity)
• Cell Line, Tumor
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Humans
• Masoprocol (analogs & derivatives, chemical synthesis, toxicity)
• Melanoma (drug therapy)
• Mice
• Xenograft Model Antitumor Assays