Flavokawains, Plant-derived Chalcones, Inhibit Differentiation of Murine Pre-adipocytes
Novriyandi Hanif, Dyah Iswantini, Yusuke Hioki, Anggia Murni, Masaki Kita, Junichi Tanaka
Abstract
Abstract Efforts to isolate compounds from an Indonesian member of the ginger family, Kaempferia angustifolia, yielded three known molecules, identified as (+)-crotepoxide (1), (+)-pipoxide chlorohydrin (2), and flavokawain A (FKA, 3). All three compounds strongly inhibited triglyceride accumulation in 3T3-L1 murine pre-adipocytes at 10 µg/mL, and compounds 1 and 2 were both cytotoxic at this concentration. To determine the biological activities of natural 3, flavokawains A (3), B (4) and C (5) were synthesized. While 4 was cytotoxic, both 3 and 5 potently inhibited differentiation of murine pre-adipocytes and reduced triglyceride accumulation (EC50 = 64.4 and 26.1 µM, respectively) with relatively weak cytotoxicity. Thus, the electron-donating group on the aromatic B ring may contribute to the highly selective anti-obesity activity.