Marinobazzanan, a Bazzanane-Type Sesquiterpenoid, Suppresses the Cell Motility and Tumorigenesis in Cancer Cells

Marinobazzanan (<b>1</b>), a new bazzanane-type sesquiterpenoid, was isolated from a marine-derived fungus belonging to the genus <i>Acremonium</i>. The chemical structure of <b>1</b> was elucidated using NMR and mass spectroscopic data, while the relative configu...

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Main Authors: Sultan Pulat, Prima F. Hillman, Sojeong Kim, Ratnakar N. Asolkar, Haerin Kim, Rui Zhou, İsa Taş, Chathurika D. B. Gamage, Mücahit Varlı, So-Yeon Park, Sung Chul Park, Inho Yang, Jongheon Shin, Dong-Chan Oh, Hangun Kim, Sang-Jip Nam, William Fenical
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:Marine Drugs
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Online Access:https://www.mdpi.com/1660-3397/21/3/153
Description
Summary:Marinobazzanan (<b>1</b>), a new bazzanane-type sesquiterpenoid, was isolated from a marine-derived fungus belonging to the genus <i>Acremonium</i>. The chemical structure of <b>1</b> was elucidated using NMR and mass spectroscopic data, while the relative configurations were established through the analysis of NOESY data. The absolute configurations of <b>1</b> were determined by the modified Mosher’s method as well as vibrational circular dichroism (VCD) spectra calculation and it was determined as 6<i>R</i>, 7<i>R</i>, 9<i>R</i>, and 10<i>R</i>. It was found that compound <b>1</b> was not cytotoxic to human cancer cells, including A549 (lung cancer), AGS (gastric cancer), and Caco-2 (colorectal cancer) below the concentration of 25 μM. However, compound <b>1</b> was shown to significantly decrease cancer-cell migration and invasion and soft-agar colony-formation ability at concentrations ranging from 1 to 5 μM by downregulating the expression level of KITENIN and upregulating the expression level of KAI1. Compound <b>1</b> suppressed β-catenin-mediated TOPFLASH activity and its downstream targets in AGS, A549, and Caco-2 and slightly suppressed the Notch signal pathway in three cancer cells. Furthermore, <b>1</b> also reduced the number of metastatic nodules in an intraperitoneal xenograft mouse model.
ISSN:1660-3397