Synthesis and evaluation of effective photoaffinity probe molecule of furospinosulin-1, a hypoxia-selective growth inhibitor.

Abstract

The synthesis and evaluation of a photoaffinity probe molecule for furospinosulin-1, a hypoxia-selective growth inhibitor that we identified from marine sponge, was studied. An analogue carrying an alkyne tail showed potent hypoxia-selective inhibitory activity exceeding that of the parent molecule, and exhibited in vivo anti-tumor activity following oral administration. The alkyne moiety in the analogue was also found to be a good anchoring group for the preparation of probe molecules; a photoaffinity probe molecule having an optimized spacer length was selected through the systematic synthesis of several probes and the evaluation of their hypoxia-selective growth inhibitory activity and electrophoretic mobility shift properties.

• Authors: Naoyuki Kotoku, Chiaki Nakata, Takashi Kawachi, Takanori Sato, Xiu-Han Guo, Aoi Ito, Yuji Sumii, Masayoshi Arai, Motomasa Kobayashi
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 22 Issue 7 Pg. 2102-12 (Apr 01 2014) ISSN: 1464-3391 [Electronic] England
• PMID: 24631363 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Photoaffinity Labels
• Sesterterpenes
• furospinosulin-1

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Humans
• Hypoxia
• Mice
• Molecular Structure
• Photoaffinity Labels (chemical synthesis, chemistry, pharmacology)
• Sesterterpenes (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship
• Tumor Cells, Cultured