Synthesis and evaluation of novel carbocyclic oxetanocin A (COA-Cl) derivatives as potential tube formation agents

2016 Fiscal Year Final Research Report

• Project/Area Number: 24790123
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Drug development chemistry
• Research Institution: Tokushima Bunri University
• Principal Investigator: Sakakibara Norikazu 徳島文理大学, 薬学部, 講師 (10441594)
• Co-Investigator(Renkei-kenkyūsha): TSUKAMOTO Ikuko 香川大学, 医学部 薬物生体情報学講座, 客員教授 (10183477) ; IGARASHI Junsuke 香川大学, 医学部 自律機能生理学講座, 准教授 (20346638)
• Project Period (FY): 2012-04-01 – 2017-03-31
• Keywords: コアクロル / 血管新生促進活性

Outline of Final Research Achievements

Six novel carbocyclic oxetanocin A analogs (2-chloro-C.OXT-A; COA-Cl) with various hydroxymethylated or spiro-conjugated cyclobutane rings at the N9-position of the 2-chloropurine moiety were synthesized and evaluated using human umbilical vein endothelial cells. All prepared compounds showed good to moderate activity with angiogenic potency. Among these compounds, 100 μM cis-trans-2',3'-bis(hydroxymethyl)cyclobutyl derivative, trans-3'-hydroxymethylcyclobutyl analog, and 3',3'-bis(hydroxymethyl)cyclobutyl derivative had greater angiogenic activity, with relative tube areas of 3.43 ± 0.44, 3.32 ± 0.53, and 3.59 ± 0.83 (mean ± SD), respectively, which was comparable to COA-Cl (3.91 ± 0.78). These data may be important for further development of this class of compounds as potential tube formation agents.

Free Research Field

創薬化学