Total synthesis and bioactivity of unique flavone desmosdumotin B and its analogs.
The first total synthesis of a unique flavone natural product, desmosdumotin B (1), was accomplished. Furthermore, three novel flavonoids, 6-8, and a novel chalcone, 9, were synthesized. The new compounds were evaluated as in vitro inhibitors of human cancer cell growth. The synthetic 1 showed significant cytotoxic activity against a multi-drug resistant cell line (KB-VIN) with an ED50 value of 2.0 microg/mL compared to >40 microg/mL against the parental KB cell line. Flavone 7 displayed selective activity against 1A9 ovarian carcinoma with an ED50 value of 0.7 microg/mL. Selected 1-analogs and synthetic intermediates were also screened for antitumor-promoting effects as inhibitors of EBV-EA activation. Among them, trihydroxyacetophenone derivatives 11 and 14 showed good activity.
Nakagawa-Goto
Kyoko
K
Natural Products Laboratory, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
Bastow
Kenneth F
KF
Wu
Jiu-Hong
JH
Tokuda
Harukuni
H
Lee
Kuo-Hsiung
KH
D000475:Alkenes / Q000737:chemistry / Q000494:pharmacology; D000956:Antigens, Viral / Q000737:chemistry* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D047309:Flavones; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007659:Ketones / Q000737:chemistry / Q000494:pharmacology; D009369:Neoplasms / Q000188:drug therapy; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000475:Alkenes; D000956:Antigens, Viral; D000970:Antineoplastic Agents; C033305:Epstein-Barr virus early antigen; D047309:Flavones; D005419:Flavonoids; D007659:Ketones; C502470:desmosdumotin C; C043562:flavone