NBRI17671, a new antitumor compound, produced by Acremonium sp. CR17671.

Abstract

The interaction between the receptor for advanced glycation end-product (RAGE) and amphoterin has an important role in tumor growth and metastasis. Because the abrogation of the interaction results in the inhibition of the tumor growth and metastasis, we designed a screening system for an inhibitor of the interaction between RAGE and amphoterin. In the course of our screening of the inhibitor, we isolated a novel natural compound NBRI17671 (1) from the fermentation broth of Acremonium sp. CR17671. We also modified 1 into a more active NBRI17671al (2). Although 1 at 50 g ml(-1) weakly inhibited binding of various cells to amphoterin, 2 at 50 g ml(-1) inhibited it by >50% of control. Compound 2 effectively inhibited the tumor growth of glioma and lung tumor xenografts in mice at 25 mg kg(-1). Furthermore, 2 was found to downregulate mitogen-activated protein kinase (MAPK) activity in the tumor cells.

• Authors: Manabu Kawada, Ihomi Usami, Tetsuya Someno, Takumi Watanabe, Hikaru Abe, Hiroyuki Inoue, Shun-ichi Ohba, Tohru Masuda, Yuji Tabata, Sho-ichi Yamaguchi, Daishiro Ikeda
• Journal: The Journal of antibiotics (J Antibiot (Tokyo)) Vol. 63 Issue 5 Pg. 237-43 (May 2010) ISSN: 1881-1469 [Electronic] England
• PMID: 20379217 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• HMGB1 Protein
• NBRI17671
• Receptor for Advanced Glycation End Products
• Receptors, Immunologic
• Tetrahydronaphthalenes
• Mitogen-Activated Protein Kinases

Topics

• Acremonium (metabolism)
• Animals
• Antibiotics, Antineoplastic (chemistry, isolation & purification, pharmacology)
• Down-Regulation (drug effects)
• Female
• Glioma (drug therapy)
• HMGB1 Protein (metabolism)
• Lung Neoplasms (drug therapy)
• Mice
• Mice, Inbred C57BL
• Mice, Inbred ICR
• Mitogen-Activated Protein Kinases (antagonists & inhibitors)
• Neoplasm Transplantation
• Neoplasms, Experimental (drug therapy)
• Receptor for Advanced Glycation End Products
• Receptors, Immunologic (antagonists & inhibitors)
• Tetrahydronaphthalenes (chemistry, isolation & purification, pharmacology)