A small oxazine compound as an anti-tumor agent: A novel pyranoside mimetic that binds to VEGF, HB-EGF, and TNF-α

Basappa and Murugan, Sengottuvelan and Kavitha, C. V. and Purushothaman, Anurag and Nevin, Kottayath G. and Sugahara, Kazuyuki and Rangappa, K. S. (2010) A small oxazine compound as an anti-tumor agent: A novel pyranoside mimetic that binds to VEGF, HB-EGF, and TNF-α. Cancer Letters, 297 (2). 231 - 243. ISSN 0304-3835

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A novel pyranoside mimetic compound, DMBO (2-(2,6-difluorophenyl)-5-(4-methoxyphenyl)-1-oxa-3-azaspiro5.5undecane), was designed and synthesized. The sugar mimicking behavior of DMBO was addressed by its ability to bind several growth factors/cytokines such as vascular endothelial growth factor (VEGF), heparin-binding epidermal growth factor-like growth factor (HB-EGF), and tumor necrosis factor (TNF)-α as demonstrated by the recently developed surface plasmon resonance assay. DMBO exhibited strong anti-proliferation activity in vitro against tumor cells including a highly metastatic murine osteosarcoma cell line LM8G7 that secretes VEGF as well as two human ovarian cell lines, OVSAHO and SKOV-3, which secrete TNF-α and HB-EGF respectively. Furthermore, DMBO inhibited the metastatic activity to the mouse liver of LM8G7 cells injected from a lateral tail vein, and affected the heparan-degrading activity of LM8G7 cells. Here, we report that DMBO acts as a human heparanase inhibitor in vitro possibly as a substrate mimetic. DMBO also inhibited the migration and invasion of LM8G7 cells and angiogenic events such as endothelial cell proliferation, migration and capillary tube-like formation in vitro. More prominently, the administration of DMBO with heparin resulted in synergistic anti-tumor effects in mouse modelofosteosarcoma. These preclinical data shows the potential anti-cancer effects of DMBO.

Item Type: Article
Uncontrolled Keywords: Tumor metastases, Heparin, Growth factors, Oxazines, Sugar mimetics
Subjects: C Chemical Science > Chemistry
Divisions: Department of > Chemistry
Depositing User: LA manjunath user
Date Deposited: 05 Jul 2019 06:07
Last Modified: 01 Jun 2023 10:52
URI: http://eprints.uni-mysore.ac.in/id/eprint/4615

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