Actinoquinazolinone, a New Quinazolinone Derivative from a Marine Bacterium Streptomyces sp. CNQ-617, Suppresses the Motility of Gastric Cancer Cells

Sultan Pulat; Da-Ae Kim; Prima F Hillman; Dong-Chan Oh; Hangun Kim; Sang-Jip Nam; William Fenical

doi:10.3390/md21090489

Actinoquinazolinone, a New Quinazolinone Derivative from a Marine Bacterium Streptomyces sp. CNQ-617, Suppresses the Motility of Gastric Cancer Cells

Mar Drugs. 2023 Sep 13;21(9):489. doi: 10.3390/md21090489.

Authors

Sultan Pulat¹, Da-Ae Kim², Prima F Hillman², Dong-Chan Oh³, Hangun Kim¹, Sang-Jip Nam², William Fenical⁴

Affiliations

¹ College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Republic of Korea.
² Department of Chemistry and Nanoscience, Ewha Womans University, Seoul 03760, Republic of Korea.
³ Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
⁴ Center of Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92093-0204, USA.

Abstract

A HPLC-UV guided fractionation of the culture broth of Streptomyces sp. CNQ-617 has led to the isolation of a new quinazolinone derivative, actinoquinazolinone (1), as well as two known compounds, 7-hydroxy-6-methoxy-3,4-dihydroquinazolin-4-one (2) and 7-methoxy-8-hydroxy cycloanthranilylproline (3). The interpretation of 1D, 2D NMR, and MS spectroscopic data revealed the planar structure of 1. Furthermore, compound 1 suppressed invasion ability by inhibiting epithelial-mesenchymal transition markers (EMT) in AGS cells at a concentration of 5 µM. In addition, compound 1 decreased the expression of seventeen genes related to human cell motility and slightly suppressed the signal transducer and activator of the transcription 3 (STAT3) signal pathway in AGS cells. Together, these results demonstrate that 1 is a potent inhibitor of gastric cancer cells.

Keywords: Streptomyces sp.; actinoquinazolinone; gastric cancer; marine natural products; motility; quinazolinone.

Grants and funding

This research was supported by the National Research Foundation of Korea, grant funded by the Korean Government (Ministry of Science and ICT; no. 2021R1A4A2001251 to S.-J.N.). Isolation of the bacterium was a result of the financial support from the US National Cancer Institute (grant CA R37044848 to W.F.).