Celludinone C, a new dihydroisobenzofuran isolated from Talaromyces cellulolyticus BF-0307

Reiko Seki; Kenichiro Nagai; Keisuke Kobayashi; Satoru Shigeno; Tatsuya Shirahata; Yoshinori Kobayashi; Taichi Ohshiro; Hiroshi Tomoda

doi:10.1038/s41429-024-00785-5

Celludinone C, a new dihydroisobenzofuran isolated from Talaromyces cellulolyticus BF-0307

J Antibiot (Tokyo). 2025 Jan;78(1):26-34. doi: 10.1038/s41429-024-00785-5. Epub 2024 Nov 14.

Authors

Reiko Seki¹, Kenichiro Nagai², Keisuke Kobayashi^{1

3}, Satoru Shigeno^{1

3}, Tatsuya Shirahata^{1

4}, Yoshinori Kobayashi^{1

4}, Taichi Ohshiro^{5

6}, Hiroshi Tomoda^{1

3}

Affiliations

¹ Medical Research Laboratories, Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
² Medical Research Laboratories, Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan. [email protected].
³ Department of Microbial Chemistry, Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
⁴ Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
⁵ Medical Research Laboratories, Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan. [email protected].
⁶ Department of Microbial Chemistry, Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan. [email protected].

PMID: 39543335
DOI: 10.1038/s41429-024-00785-5

Abstract

Celludinones A and B, isolated from the fungus Talaromyces cellulolyticus BF-0307, were inhibitors of sterol O-acyltransferase (SOAT). Further searches for their congeners in the culture broth of the fungus by LC/UV and LC/MS analysis resulted in the discovery of four structurally related compounds, including a new dihydroisobenzofuran named celludinone C (1). The structure of 1, including its absolute stereochemistry, was elucidated by 1D/2D NMR and electronic circular dichroism (ECD) spectra. All of these compounds inhibited both SOAT1 and 2, with IC₅₀ values ranging from 8.5 to 30 µM.

MeSH terms

Benzofurans* / chemistry
Benzofurans* / isolation & purification
Benzofurans* / pharmacology
Circular Dichroism
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / isolation & purification
Enzyme Inhibitors / pharmacology
Humans
Inhibitory Concentration 50
Magnetic Resonance Spectroscopy
Mass Spectrometry
Molecular Structure
Sterol O-Acyltransferase / antagonists & inhibitors
Talaromyces* / chemistry

Substances

Benzofurans
Sterol O-Acyltransferase
Enzyme Inhibitors