Unusual Vilasinin-Class Limonoids from <i>Trichilia rubescens</i>
Saidanxia Amuti,
Yohei Saito,
Shuichi Fukuyoshi,
Katsunori Miyake,
David J. Newman,
Barry R. O’Keefe,
Kuo-Hsiung Lee,
Kyoko Nakagawa-Goto
Affiliations
Saidanxia Amuti
School of Pharmaceutical Sciences, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-1192, Japan
Yohei Saito
School of Pharmaceutical Sciences, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-1192, Japan
Shuichi Fukuyoshi
School of Pharmaceutical Sciences, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-1192, Japan
Katsunori Miyake
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji 192-0392, Japan
David J. Newman
Natural Products Branch, Developmental Therapeutics Program, Center of Cancer Research, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick, MD 21702-1201, USA
Barry R. O’Keefe
Natural Products Branch, Developmental Therapeutics Program, Center of Cancer Research, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick, MD 21702-1201, USA
Kuo-Hsiung Lee
Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7568, USA
Kyoko Nakagawa-Goto
School of Pharmaceutical Sciences, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-1192, Japan
Eight vilasinin-class limonoids, including the unusually chlorinated rubescins K–M (1–3), the 2,3-epoxylated rubescin N (4), and rubescins O–R (5–8), were newly isolated from Trichilia rubescens. The structures of the isolated compounds were determined through spectroscopic and spectrometric analyses, as well as ECD calculations. The natural occurrence of chlorinated limonoids 1–3 was confirmed by chemical methods and HPLC analysis of a roughly fractionated portion of the plant extract. Eight selected limonoids, including previously known and new compounds, were evaluated for antiproliferative activity against five human tumor cell lines. All tested limonoids, except 8, exhibited significant potency, with IC50 values of 14 strongly inhibited tumor cell growth, with IC50 values of 0.54–2.06 μM against all tumor cell lines, including multi-drug-resistant cells.
