Four New Macrocyclic Trichothecenes from Two Strains of Marine-derived Fungi of the Genus Myrothecium

Jinzhong Xu, Azusa Takasaki, Hisayoshi Kobayashi, Taiko Oda, Junko Yamada, Remy E. P. Mangindaan, Kazuyo Ukai, Hiroshi Nagai, Michio Namikoshi

Dedicated to the memory of Professor Kenneth L. Rinehart.

Received: March 20, 2006 / Accepted: May 16, 2006
© Japan Antibiotics Research Association

Abstract Three new macrocyclic trichothecenes, named 12´-hydroxyroridin E (1), roridin Q (2), and 2´,3´-deoxyroritoxin D (3), were isolated from the marine-derived fungus Myrothecium roridum TUF 98F42, and a new macrocyclic trichothecene, named roridin R (4), was isolated from Myrothecium sp. TUF 02F6 together with roridins A and H and isororidin E. The structures of new compounds were determined on the basis of their spectral data. Compound 2 possessed a unique ether moiety at the 13´ position of 1. Compound 4 was a 2´,3´-dihydro-2´-hydroxy derivative of roridin H. The IC50 values of compounds 1, 2, and 4 against the murine leukemia cell line L1210 were 0.19, 31.2, and 0.45 μM, respectively. Compound 3 showed antiyeast activity to Saccharomyces cerevisiae at 1 μg/disc (inhibition zone: 12.2 mm), which was about 10 time more active than roritoxin D (10.2 mm at 10 μg/disc).

Keywords Myrothecium roridum, marine-derived fungus, roridin Q, roridin R, macrocyclic trichothecene, cytotoxicity, L1210

M. Namikoshi (Corresponding author), J. Xu, A. Takasaki, K. Ukai, H. Nagai: Department of Ocean Sciences, Tokyo University of Marine Science and Technology, Minato-ku, Tokyo 108-8477, Japan, E-mail: mnami@tohoku-pharm.ac.jp
H. Kobayashi: Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan
T. Oda, J. Yamada: Faculty of Pharmaceutical Sciences, Kyoritsu University of Pharmacy, Minato-ku, Tokyo 105-8512, Japan
R. E. P. Mangindaan: Faculty of Fisheries and Marine Science, Sam Ratulangi University, Kampus Bahu, Manado 95115, Indonesia
Present address: Tohoku Pharmaceutical University, Komatsushima, Aoba-ku, Sendai 981-8558, Japan