| 著者：別形式 | Kurihara, Teruo / Noguchi, Mayumi / Noguchi, Takashi / Wakabayashi, Hidetsugu / Motohashi, Noboru / Sakagami, Hiroshi |
| 著者：所属(別形式） | Josai University, Faculty of Science, Department of Chemistry / Josai University, Faculty of Science, Department of Chemistry / Josai University, Faculty of Science, Department of Chemistry / Josai University, Faculty of Science, Department of Chemistry / Meiji Pharmaceutical University / Meikai University School of Dentistry |
| 抄録 | The structure-activity relationship of the cytotoxicactivity of azulene and azulene derivatives was discussed,using theoretically calculated results. In order to clearly dividethe azulenes into three groups according to their functionalgroups, the CC50, four different dipole moments (μG, μESP-G, μW and μESP-W) and heats of formation (ΔHf) of the azulenes[1-24] were separately calculated in two states, gas-phase andwater, by the conductor-like screening model/parametricmethod 3 (COSMO/PM3). For the halogenated azulenes andisopropyl azulenes, the cytotoxic activity might follow thethree quantitative structure-activity relationship (QSAR)parameters: ΔΔHf, HOMO energy and μw. Whereas, for theother ten compounds [3-5, 7-8, 10, 15-18], the cytotoxicactivity might be related to the three QSAR parameters, ΔΔHf,LUMO energy and μG.Azulene chemistry, including synthesis and their physicaland chemical properties, has been extensively studied formore than four decades (1-4). Azulene derivatives haveshown interesting biological activities, such as antibacterial(5), anti-ulcer (6) and relaxant activities (7), inhibition ofthromboxane A2-induced vasoconstriction and thrombosis(8), acute toxicity and local anesthetic activity (9).In our previous paper, the cytotoxicities of 27 azulenederivatives against three human normal cell lines and threehuman oral tumor cell lines were discussed (10). Amongsix halogenated azulenes, 1,3-dibromoazulene [13] wasfound to be highly cytotoxic against both human tumorcells [CC50 (HSG)=0.31 mM; CC50 (HSC-2)=0.19 mM;CC50 (HSC-3)=0.15 mM] and normal human cells [CC50 (HGF)=0.27 mM; CC50 (HPC)=0.26 mM; CC50(HPLF)=0.30 mM]. Among seven isopropylazulenederivatives, methyl 7-isopropyl-2-methoxyazulene-1-carboxylate [24] was comparably cytotoxic against thetumor cell lines [CC50 for HSG, HSC-2 and HSC-3=0.11mM], but showed much lower cytotoxicity against normalcells. (10). This tumor-specific cytotoxic activity might berelated to the position of functional groups. The azulenescan be conveniently divided into three groups based ontheir functional groups: halogenated azulene derivatives,isopropylazulene derivatives and other derivatives.Azulene [1] is considered to be the reference compound.Based on a molecular orbital calculation concerning thephysicochemical parameters and the cytotoxic activities ofazulene derivatives, the purpose of this paper was topresent some relationships between the electronicstructure and the cytotoxic activity of azulene derivatives. |
