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Drimane sesquiterpene esters produced by Aspergillus insuetus BF-1613 as inhibitors of sterol O-acyltransferase

The Journal of Antibiotics volume 77, pages 837–841 (2024)Cite this article

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Abstract

A new drimane sesquiterpene ester, designated insuetusolate (1), and four reported ones (2–5) were isolated from a culture broth of Aspergillus insuetus BF-1613. The chemical structure of 1 was elucidated by extensive spectroscopic analyses, including MS and NMR. Compound 1 has a drimane-type sesquiterpene core with a 2’E,4’E,6’E-octatrienoate side chain. All these drimane sesquiterpene esters inhibited both sterol O-acyl transferase 1 (SOAT1) and 2 (SOAT2), but exhibited slightly potent inhibition against SOAT1 than SOAT2 with selectivity index (SI) [log (IC50 for SOAT1/ IC50 for SOAT2)] values ranging from −0.24 to −0.94.

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Acknowledgements

We are grateful to Noriko Sato, Dr. Kenichiro Nagai and Reiko Seki of Graduate School of Pharmaceutical Sciences, Kitasato University for the measurements of NMR and MS spectra and the late Prof. L.L. Rudel of Wake Forest University, Winston-Salem, NC, USA for kindly providing SOAT1-CHO and SOAT2-CHO cells. This work was financially supported by JSPS KAKENHI Grant numbers 18KK0219 (Fund for the Promotion of Joint International Research (Fostering Joint International Research (B)) (HT), MEXT Scholarship (EAAN) and Kitasato University Research Grant for Young Researcher (EAAN).

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Authors and Affiliations

  1. Department of Microbial Chemistry, Graduate School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan

    Elyza Aiman Azizah Nur, Keisuke Kobayashi, Rio Tejima, Hiroshi Tomoda & Taichi Ohshiro

  2. Medicinal Research Laboratories, School of Pharmacy, Kitasato University, Tokyo, Japan

    Elyza Aiman Azizah Nur, Keisuke Kobayashi, Hiroshi Tomoda & Taichi Ohshiro

  3. Department of Microbial Chemistry, School of Pharmacy, Kitasato University, Tokyo, Japan

    Elyza Aiman Azizah Nur, Keisuke Kobayashi, Yosuke Katada, Hiroshi Tomoda & Taichi Ohshiro

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  1. Elyza Aiman Azizah Nur
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  2. Keisuke Kobayashi
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Correspondence to Taichi Ohshiro.

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Nur, E.A.A., Kobayashi, K., Tejima, R. et al. Drimane sesquiterpene esters produced by Aspergillus insuetus BF-1613 as inhibitors of sterol O-acyltransferase. J Antibiot 77, 837–841 (2024). https://doi.org/10.1038/s41429-024-00774-8

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