Synthesis, characterization, and anti-melanoma activity of tetra-O-substituted analogs of nordihydroguaiaretic acid.
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.
Meyers
Ross O
RO
University of Arizona Cancer Center, Tucson, AZ 85724, USA. rom9765@hotmail.com
Lambert
Joshua D
JD
Hajicek
Nicole
N
Pourpak
Alan
A
Kalaitzis
John A
JA
Dorr
Robert T
RT
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009637:Masoprocol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000633:toxicity; D008545:Melanoma / Q000188:drug therapy*; D051379:Mice; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D009637:Masoprocol