TY - JOUR
T1 - Structure-related cytotoxic activity of derivatives from kulokekahilide-2, a cyclodepsipeptide in Hawaiian marine mollusk
AU - Umehara, Masahiro
AU - Negishi, Takayuki
AU - Tashiro, Tomoko
AU - Nakao, Yoichi
AU - Kimura, Junji
N1 - Funding Information:
This study was supported mainly by the Research Institute of Aoyama Gakuin and partially by the Grant-in-Aid for Young Scientists (A) (23681010), the Ministry of Education, Culture, Sports, Science and Technology, Japan and the Japan Society for the Promotion of Science, Japan.
PY - 2012/12/15
Y1 - 2012/12/15
N2 - Kulokekahilide-2, a 26-membered cyclodepsipeptide, was isolated from Hawaiian marine mollusk and possessed potent cytotoxicity in mammalian tumor cells. In the present study, we synthesized kulokekahilide-2 and its derivatives and examined the structure-activity relationships of these peptides in human cancer cells (A549, K562, and MCF7 cells). This study demonstrated that the cyclization of depsipeptide and the chirality of the 21 position in Ala in kulokekahilide-2 were important for its cytotoxic property and that addition of halogen at the para position of phenyl group in the 24-d-MePhe in kulokekahilide-2 as well as some derivatives remarkably increased their cytotoxicity in human cancer cells. These results suggest that the modifications of 24-d-MePhe in kulokekahilide-2, preserving its cyclization and the chirality at the 21-position, are promising strategy for exploring new derivative of kulokekahilide-2 as anti-tumor drug.
AB - Kulokekahilide-2, a 26-membered cyclodepsipeptide, was isolated from Hawaiian marine mollusk and possessed potent cytotoxicity in mammalian tumor cells. In the present study, we synthesized kulokekahilide-2 and its derivatives and examined the structure-activity relationships of these peptides in human cancer cells (A549, K562, and MCF7 cells). This study demonstrated that the cyclization of depsipeptide and the chirality of the 21 position in Ala in kulokekahilide-2 were important for its cytotoxic property and that addition of halogen at the para position of phenyl group in the 24-d-MePhe in kulokekahilide-2 as well as some derivatives remarkably increased their cytotoxicity in human cancer cells. These results suggest that the modifications of 24-d-MePhe in kulokekahilide-2, preserving its cyclization and the chirality at the 21-position, are promising strategy for exploring new derivative of kulokekahilide-2 as anti-tumor drug.
KW - Cyclodepsipeptide
KW - Cytotoxic activity
KW - Kulokekahilide-2
KW - Structure-activity relationship
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U2 - 10.1016/j.bmcl.2012.10.058
DO - 10.1016/j.bmcl.2012.10.058
M3 - Article
C2 - 23127885
AN - SCOPUS:84870252626
SN - 0960-894X
VL - 22
SP - 7422
EP - 7425
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 24
ER -
