RT Journal Article SR Electronic T1 The Anticancer Effects of Novel α-Bisabolol Derivatives Against Pancreatic Cancer JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 589 OP 598 VO 37 IS 2 A1 YOSHIHIKO MURATA A1 TOSHIO KOKURYO A1 YUKIHIRO YOKOYAMA A1 JUNPEI YAMAGUCHI A1 TOMOHIRO MIWA A1 MASATOSHI SHIBUYA A1 YOSHIHIKO YAMAMOTO A1 MASATO NAGINO YR 2017 UL http://ar.iiarjournals.org/content/37/2/589.abstract AB Pancreatic cancer is highly malignant, characterized by aggressive proliferation, invasion, and metastasis. α-Bisabolol is an oily sesquiterpene alcohol derived from a variety of plants. We previously demonstrated that α-bisabolol is a potential therapeutic agent for pancreatic cancer. The aim of this study was to develop α-bisabolol derivatives which are more potent than the parent compound and may be clinically useful against pancreatic cancer. First, 22 derivatives of α-bisabolol were designed and synthesized. α-Bisabolol derivatives 4 and 5 had more potent inhibitory effects on the proliferation of pancreatic cancer cells than did α-bisabolol. Next, 15 additional α-bisabolol derivatives were designed and synthesized based on the structure of α-bisabolol derivatives 4 and 5. Among them, α-bisabolol derivative 5 had the strongest inhibitory effect on proliferation. This novel compound reduced the proliferation of various pancreatic cancer cell lines, such as KLM1, Panc1, and KP4. In addition, the compound induced higher levels of apoptosis in pancreatic cancer cell lines than did α-bisabolol. α-Bisabolol derivative 5 inhibited xenograft tumor growth and reduced dissemination of pancreatic cancer to peritoneal nodules. The compound strongly suppressed AKT expression in the peritoneal nodules. Reduced AKT expression in peritoneal nodules is consistent with an anticancer effect. These data indicate that α-bisabolol derivative 5 effectively prevents the progression of pancreatic cancer via inhibition of AKT. Taken together, the results showed that this compound has attractive therapeutic properties as a novel anticancer drug for pancreatic cancer.