@article{1dafad99a36f43259e2c8ec5c8921658,
title = "Tokaramide A, a new cathepsin B inhibitor from the marine sponge Theonella aff. mirabilis",
abstract = "A new cathepsin B inhibitor, tokaramide A (1) has been isolated from the marine sponge Theonella aff. mirabilis. Its structure was determined by spectroscopic and chemical methods. Tokaramide A inhibits cathepsin B with an IC50 value of 29.0 ng / mL.",
keywords = "Enzyme inhibitors, Marine metabolites, Natural products, Peptides and polypeptides",
author = "Nobuhiro Fusetani and Masaki Fujita and Yoichi Nakao and Shigeki Matsunaga and {Van Soest}, {Rob W.M.}",
note = "Funding Information: (1.0 mg) was added, and the mixture was stirred for 2 h at 30 °C. After addition of 100 vtL of 0.5 N HCI to the reaction mixture, the solution was dried in a stream of N v The residue was hydrolyzed with 6 N HCI at 105 °C for 12 h. After removal of HC1 in a stream of N2, 50 ~tL of 0.1% 1-fluoro-2, 4-dinitrophenyl-5-L-alanine amide (L-FDAA) in acetone and 100 ~tL of 0.1 M NaHCO3 were added to the hydrolysate, and the mixture heated at 80 °C for 10 min. To the reaction mixture were added 50 ~tL of 0.2 N HCI and 100 ~L of 50% aq. MeCN containing 0.05% TFA, and 20 ~tL of aliquots of the mixture subjected to HPLC analysis \[COSMOSIL 5C18-MS (dp 4.6 x 250 mm); mobile phase, aq. MeCN containing 50 mM NH,OAc\]. Acknowledgment We thank Professor P. J. Scheuer of university of Hawaii for editorial comments. This work was partly supported by a Grant-in-Aid from the Ministry of Education, Science, Culture, and Sports of Japan and Japan Society for the Promotion of Science, {"}Research for the Future Program{"} (JSPS-RFTF) References 1. Part 98 of the Bioactive Marine Metabolites Series. Part 97: Tsukamoto, S.; Matsunaga, S.; Fusetani, N.; Toh-e, A~ Tetrahedron, 1999, 55, 13697-13702. 2. Otto, H.-H.; Shirmeister, T. Chem. Rev., 1997, 97, 133-171. 3. The name was coined fi'om the name of the collection site. 4. Kupchan, S. M.; Britton, R. W.; Ziegler, M. E; Sigel, C. W. J. Org. Chem. 1973, 38, 178-179. 5. Edwards, M. W.; Bax, A. J. Am. Chem. Soc. 1986, 108, 918-923. 6. Summers, M. E; Marzilli, L. G.; Bax, A. J. Am. Chem. Soc. 1986, 108, 4285-4294. 7. Bax, A.; Azolos, A.; Dinya, Z.; Sudo, K. J. Am. Chem. Soc. 1986, 108, 8056-8063. 8. Schultz, R. M.; Varma-Nelson, P.; Oritz, R.; Kozlowski, K. A.; Orawski, A. T.; Pagast, P.; Frankfater, A. J. Biol. Chem. 1989, 264, 3, 1497-1507. 9. Bothner-By, A. A.; Stephens, R. L.; Lee, J.; Warren, C. D.; Jeanloz, R. W. J. Am. Chem. Soc. 1984, 106, 811-813. 10. Ikeda, I.; Umino, M.; Okahara, M.J. Org. Chem. 1986, 51,569-571. 11. Nakao, Y.; Oku, N.; Matsunaga, S.; Fusetani, N. J. Nat. Prod. 1998, 61,667-670. 12. Marfey, P. CarlsbergRes. Commun. 1984, 49, 591-596. 13. Maeda, K.; Kawamura, K.; Kondo, S.; Aoyagi, T.; Takeuti, T.; Umezawa, H. J. Antibiot. 1971, 24, 6, 402-404. 14. Hanada, K.; Tamai, M.; Yamaguchi, M.; Ohmura, S.; Sawada, J.; Tanaka, I. Agric. Biol. Chem. 1978, 42, 523-528. 15. Hiwasa, T.; Fujita-Yoshigaki, J.; Shirouzu, M.; Koide. H.; Sawada, T.; Sakiyama, S.; Yokoyama, S. Cancer Lett. 1993, 69, 161-165.",
year = "1999",
month = dec,
day = "20",
doi = "10.1016/S0960-894X(99)00618-6",
language = "English",
volume = "9",
pages = "3397--3402",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Elsevier Ltd",
number = "24",
}
