1373922-46-3Relevant academic research and scientific papers
Synthesis and biological evaluation of the 12,12-dimethyl derivative of aplog-1, an anti-proliferative analog of tumor-promoting aplysiatoxin
Nakagawa, Yu,Kikumori, Masayuki,Yanagita, Ryo C.,Murakami, Akira,Tokuda, Harukuni,Nagai, Hiroshi,Irie, Kazuhiro
, p. 1167 - 1173 (2011)
Aplog-1 is a unique analog of tumor-promoting aplysiatoxin that inhibits tumor-promotion by phorbol diesters and proliferation of tumor cells. While the structural features relevant to the biological activities of Aplog-1 remain to be identified, recent studies by us have suggested that local hydrophobicity around the spiroketal moiety of Aplog-1 is a crucial determinant of its anti-proliferative activity. This hypothesis led us to design 12,12-dimethyl-Aplog-1 (3), in which a hydrophobic geminal dimethyl group is installed proximal to the spiroketal moiety to improve biological potency. As expected, 3 was more effective than Aplog-1 in inhibiting cancer cell growth and binding to protein kinase Cδ, a putative receptor responsible for the biological response of Aplog-1. Moreover, an induction test on Epstein-Barr virus early antigen demonstrated 3 to be a better anti-tumor promoter than Aplog-1. These results indicate that 3 is a superior derivative of Aplog-1, and thus a more promising lead for anti-cancer drugs.
