TY - JOUR
T1 - New analogue of arenastatin A, a potent cytotoxic spongean depsipeptide, with anti-tumor activity
AU - Murakami, Nobutoshi
AU - Tamura, Satoru
AU - Koyama, Kouhei
AU - Sugimoto, Masanori
AU - Maekawa, Ryuji
AU - Kobayashi, Motomasa
N1 - Funding Information:
The authors are grateful to Messrs Naomi Uchida and Tohru Wada, Shionogi Research Laboratories, for in vivo experiment. This study was financially supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan. The authors are also grateful to the Naito Foundation and the Hoh-ansha Foundation for financial support.
PY - 2004/5/17
Y1 - 2004/5/17
N2 - Two analogues possessing steric hindered substituents on C-15 of arenastatin A (1), a potent cytotoxic spongean depsipeptide, were synthesized and shown to enhance stability in mouse serum. Notably, 15-tert-butylanalogue (6) with higher cytotoxicity exhibited in vivo anti-tumor activity through iv administration different from 1. Additionally, conformation analysis among the two analogues and arenastatin A (1) indicated that the torsion angle from C-14 to C-20 is a conclusive factor for the potent cytotoxicity of 1.
AB - Two analogues possessing steric hindered substituents on C-15 of arenastatin A (1), a potent cytotoxic spongean depsipeptide, were synthesized and shown to enhance stability in mouse serum. Notably, 15-tert-butylanalogue (6) with higher cytotoxicity exhibited in vivo anti-tumor activity through iv administration different from 1. Additionally, conformation analysis among the two analogues and arenastatin A (1) indicated that the torsion angle from C-14 to C-20 is a conclusive factor for the potent cytotoxicity of 1.
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U2 - 10.1016/j.bmcl.2004.02.080
DO - 10.1016/j.bmcl.2004.02.080
M3 - Article
C2 - 15109660
AN - SCOPUS:1942502673
VL - 14
SP - 2597
EP - 2601
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 10
ER -