著者

AKIRA NAKAGAWA HIROSHI TOMODA MAI VAN HAO KEIKO OKANO YUZURU IWAI SATOSHI OMURA

出版者

JAPAN ANTIBIOTICS RESEARCH ASSOCIATION

雑誌

The Journal of Antibiotics (ISSN:00218820)

巻号頁・発行日

vol.38, no.8, pp.1114-1115, 1985 (Released:2006-04-19)

参考文献数

6

被引用文献数

22 22

著者

Miyuki Konya Shiho Arima Daiki Lee Masaki Ohtawa Kenta Shimoyama Takashi Fukuda Ryuji Uchida Hiroshi Tomoda Noriyuki Yamaotsu Nobutada Tanaka Tohru Nagamitsu

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.70, no.4, pp.261-268, 2022-04-01 (Released:2022-04-01)

参考文献数

19

被引用文献数

3

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Habiterpenol is a G2 checkpoint inhibitor isolated from the culture broth of Phytohabitans sp. 3787_5. Here, we report the synthesis of new habiterpenol analogs through the total synthesis process of habiterpenol and evaluating the analogs for G2 checkpoint inhibitory activity. We investigated two different synthetic approaches for total synthesis, with intramolecular conjugate addition and Ti(III)-mediated radical cyclization as key reactions. Although the former was unsuccessful, the latter reaction facilitated stereoselective total synthesis and determination of the absolute configuration of habiterpenol. The extension of these chemistries to a structure–activity relationship (SAR) study gave new habiterpenol analogs, which could not be derived from natural habiterpenol and only be synthesized by applying the total synthesis. Therefore, this study provides important insights into SAR studies of habiterpenol.

著者

Yoko Takahashi Shogo Katoh Noriyasu Shikura Hiroshi Tomoda Satoshi Omura

出版者

Applied Microbiology, Molecular and Cellular Biosciences Research Foundation

雑誌

The Journal of General and Applied Microbiology (ISSN:00221260)

巻号頁・発行日

vol.49, no.4, pp.263-266, 2003 (Released:2005-03-18)

参考文献数

11

被引用文献数

21 32

著者

Akiho Yagi Hiroyuki Yamazaki Takeshi Terahara Taehui Yang Hiroshi Hamamoto Chiaki Imada Hiroshi Tomoda Ryuji Uchida

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Drug Discoveries & Therapeutics (ISSN:18817831)

巻号頁・発行日

vol.14, no.6, pp.287-295, 2020-12-31 (Released:2021-01-23)

参考文献数

31

被引用文献数

5

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In vivo-mimic silkworm infection models with Mycobacterium avium and Mycobacterium intracellulare were newly established to evaluate the therapeutic effects of anti-M. avium complex (MAC) antibiotics. Silkworms raised at 37°C died within 72 hours of an injection of M. avium or M.intracellulare (2.5 × 107 colony-forming unit (CFU)/larva·g) into the hemolymph. Clinical anti-mycobacterial (tuberculosis) antibiotics were evaluated under these conditions. Clarithromycin, kanamycin, streptomycin, amikacin, and ciprofloxacin exerted therapeutic effects in a dose-dependent manner, which was consistent with those in the mouse model. Furthermore, three effective actinomycete culture broths were selected in the screening program of our microbial broth library using the silkworm model, and four active metabolites, ohmyungsamycins A and B (1 and 2), chartreusin (3), and griseoviridin (4), were identified. Among these compounds, 1 showed the lowest 50% effective dose (ED50) value (8.5 µg/larva·g), while 3 had the best ED50/minimum inhibitory concentration (MIC) ratio (7.4). These results indicate that silkworm models are a useful tool for identifying anti-MAC antibiotics candidates with veritable therapeutic effects.