Synthesis and Evaluation of Novel Carbocyclic Oxetanocin A (COA-Cl) Derivatives as Potential Tube Formation Agents.
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.
Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University.
Norikazu
N
Sakakibara
Junsuke
J
Igarashi
Maki
M
Takata
Yosuke
Y
Demizu
Takashi
T
Misawa
Masaaki
M
Kurihara
Ryoji
R
Konishi
Yoshihisa
Y
Kato
Tokumi
T
Maruyama
Ikuko
I
Tsukamoto
D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D020533:Angiogenesis Inhibitors; C051061:oxetanocin; D000225:Adenine