Synthesis and structure-activity relationships for cytotoxicity and apoptosis-inducing activity of (+)-halichonine B.
Halichonine B is a sesquiterpene alkaloid isolated from the marine sponge Halichondria okadai Kadota. Halichonine B has exhibited cytotoxicity against mammalian cancer cells and induced apoptosis in the human leukemia cell line HL60. Here we established a practical route for the synthesis of halichonine B and its analogues, and we evaluated their biological activities. It was revealed that the secondary amino groups in the side chain portion are important for the strong cytotoxicity of halichonine B and that the N(11)-prenyl group is unimportant. Halichonine B and its analogues were also observed to induce apoptosis in HL60 cells.
Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan. ichiro.hayakawa@okayama-u.ac.jp.
Ichiro
I
Hayakawa
Tomomi
T
Nakamura
Osamu
O
Ohno
Kiyotake
K
Suenaga
Hideo
H
Kigoshi
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy; D011161:Porifera / Q000737:chemistry*; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000470:Alkaloids; D000970:Antineoplastic Agents; D012717:Sesquiterpenes; C000609240:halichonine B