title: Role of the phenolic hydroxyl group in the biological activities of simplified analogue of aplysiatoxin with antiproliferative activity.
abstract: The 18-deoxy derivative (3) of a simplified analogue (1) of aplysiatoxin with antiproliferative activity was synthesized to examine the role of the phenolic hydroxyl group at position 18 in the biological activities of 1. Compound 3 as well as 1 showed significant affinity for protein kinase Cδ (PKCδ), and the antiproliferative activity of 3 was slightly higher than that of 1. However, the anti-tumor-promoting activity of 3 was less than that of 1 in vitro, suggesting that the phenolic hydroxyl group of 1 is necessary for the anti-tumor-promoting activity but not for the binding of PKCδ and antiproliferative activity. Moreover, PKC isozyme selectivity of 3 was similar to that of 1, suggesting non-PKC receptors for these compounds to play some roles in the anti-tumor-promoting activity of 1.
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
authors.forename: Ryo C
authors.initials: RC
authors.lastname: Yanagita
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kamachi
authors.forename: Keisuke
authors.initials: K
authors.lastname: Tanaka
authors.forename: Akira
authors.initials: A
authors.lastname: Murakami
authors.forename: Yu
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Harukuni
authors.initials: H
authors.lastname: Tokuda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagai
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Irie
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D017665:Hydroxyl Radical / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008235:Lyngbya Toxins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy; D011493:Protein Kinase C / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D008235:Lyngbya Toxins; D017665:Hydroxyl Radical; C006610:aplysiatoxin; D011493:Protein Kinase C