B-Ring-modified and/or 5-demethylated nobiletin congeners: Inhibitory activity against pro-MMP-9 production

…, Y Okuyama, Y Miyata, H Kosano, H Takahashi…

Index: Oshitari, Tetsuta; Okuyama, Yuji; Miyata, Yoshiki; Kosano, Hiroshi; Takahashi, Hideyo; Natsugari, Hideaki Bioorganic and Medicinal Chemistry, 2011 , vol. 19, # 23 p. 7085 - 7092

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Citation Number: 8

Abstract

Three metabolites and 12 analogues of nobiletin (1) were synthesized. Whereas nobiletin derivatives 2–4 inhibited pro-MMP-9 production similarly in both PMA-and TNF-α-stimulated human lens epithelial cells, the 2′-hydroxylated analogue 5a exerted marked inhibitory effects (IC50: 0.4 μM) on PMA-treated cells, which were 170-fold more potent than those on TNF-α-treated cells. This activity may be closely related to PKC-mediated transcriptional ...