新型碳环氧杂环丁烷霉素A（COA-Cl）衍生物作为潜在血管生成剂的合成与评价

Synthesis and Evaluation of Novel Carbocyclic Oxetanocin A (COA-Cl) Derivatives as Potential Tube Formation Agents.

作者信息

Sakakibara Norikazu, Igarashi Junsuke, Takata Maki, Demizu Yosuke, Misawa Takashi, Kurihara Masaaki, Konishi Ryoji, Kato Yoshihisa, Maruyama Tokumi, Tsukamoto Ikuko

机构信息

Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University.

出版信息

Chem Pharm Bull (Tokyo). 2015;63(9):701-9. doi: 10.1248/cpb.c15-00386.

DOI:10.1248/cpb.c15-00386

PMID:26329863

Abstract

Six novel carbocyclic oxetanocin A analogs (2-chloro-C.OXT-A; COA-Cl) with various hydroxymethylated or spiro-conjugated cyclobutane rings at the N(9)-position of the 2-chloropurine moiety were synthesized and evaluated using human umbilical vein endothelial cells. All prepared compounds (2a-f) showed good to moderate activity with angiogenic potency. Among these compounds, 100 µM cis-trans-2',3'-bis(hydroxymethyl)cyclobutyl derivative (2b), trans-3'-hydroxymethylcyclobutyl analog (2d), and 3',3'-bis(hydroxymethyl)cyclobutyl derivative (2e) had greater angiogenic activity, with relative tube areas of 3.43±0.44, 3.32±0.53, and 3.59±0.83 (mean±standard deviation (S.D.)), 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.

摘要

合成了六种新型碳环氧杂环丁烷A类似物（2-氯-C.OXT-A；COA-Cl），它们在2-氯嘌呤部分的N(9)位带有各种羟甲基化或螺共轭环丁烷环，并使用人脐静脉内皮细胞进行了评估。所有制备的化合物（2a-f）均表现出良好至中等的血管生成活性。在这些化合物中，100 µM顺反-2',3'-双（羟甲基）环丁基衍生物（2b）、反式-3'-羟甲基环丁基类似物（2d）和3',3'-双（羟甲基）环丁基衍生物（2e）具有更强的血管生成活性，相对管面积分别为3.43±0.44、3.32±0.53和3.59±0.83（平均值±标准差（S.D.）），与COA-Cl（3.91±0.78）相当。这些数据对于将这类化合物进一步开发为潜在的血管生成剂可能具有重要意义。