Hidetsugu Wakabayashi

Factors that Affect the Type of Cell Death Induced by Chemicals

Surveying about 1000 compounds, we found that several low molecular weight α,β-unsaturated ketones induced non-apoptotic cell death characterized by the formation of autophagosomes, occasionally accompanied by mitochondrial shrinkage. The cytotoxic activity of these compounds was significantly reduced by the addition of N-acetyl-L-cysteine, suggesting their interaction with SH groups of intracellular targeted molecules (the so-called “non-sterically hindered Michael acceptor”). This suggests that the nature of the chemical structure as well as the type of target cells is another factor that determines the type of cell death induced by chemicals. Addendum to: Tumor-Specificity and Type of Cell Death Induced by Trihaloacetylazulenes in Human Tumor Cell Lines T. Sekine, J. Takahashi, M. Nishishiro, A. Arai, H. Wakabayashi, T. Kurihara, M. Kobayashi, K. Hashimoto, H. Kikuchi, T. Katayama, Y. Kanda, S. Kunii, N. Motohashi and H. Sakagami Anticancer Res 2007; 27:133-44

A convenient, one-pot azulene synthesis from cyclohepta[b]furan-2-ones and vinyl ether and its analogues. II: Acetals as reagent

Title synthesis by the reaction of cyclohepta[b]-furan-2-ones with acetals of several aldehydes and ketones on heating at 160-190 o C in neat or aprotic solvent

A convenient, one-pot synthesis of azulenes having versatile functional groups by the reaction of 2H-cyclohepta[b]furan-2-ones with furan derivatives

2-Acylmethyl- and 2-methoxycarbonylmethylazulene derivatives having versatile functional groups in the side chain, are synthesized in one-pot by the reaction of 2H-cyclohepta [b] furan-2-ones with furans on heating at 160-190 ° C in aprotic solvent

Synthesis of 1,2-azulenequinone derivatives by bromine-oxidation

Treatment of 2-hydroxyazulene (la) with 3 equiv. of C 5 H 5 N·HBr 3 in aqueous THF-AcOH at 0 °C for 1 h afforded l,l,3-tribromoazulene-2-one (5a). 3-Bromo-l,2-azulenequinone (2a) was obtained by the hydrolysis of 5a in the presence of Ag 2 O. Annulated compound 6 was readily obtained by the reaction of 2a with o-phenylenediamine.

One-pot synthesis of tropocoronands having heteroatoms in linker chains and related podands

Treatment of benzo[b]cyclohepta[e][1,4]oxazine (4) with 1.2 equiv. of dipropylenetriamine (5a) in ethanol at 80 °C gave 6,7,8,9,11,12,13,20,- 21,22,23,25,26,27-tetradecahydrodicyclohepta[b,m][1,4,8,12,15,19]hexa- azacyclodocosine (7a). Similar reactions of (4) with N,N-bis(3-amino- propyl)methylamine (5b), bis(3-aminopropyl) ether (5c), 1,2-bis(2-amino- ethoxy)ethane (6b), and cystamine (6c) afforded similar tropocoronands (7b, 7c, 8a, and 8b), respectively, while the reactions of (4) with an excess of these amines gave the corresponding tropopodands (11a, 11b, 11c, 12a, and 12b). The reaction of (4) with diethylenetriamine (6a) yielded tricyclic compound (10) via bicyclic pyrazino compound (9). A single-crystal X-ray diffraction analysis of the nickel(II)-complex (13) obtained from (7a) was made

Multidrug Resistance Reversal on Cancer Cells by Selected Carotenoids, Flavonoids and Anthocyanins

The multidrug resistance (MDR) proteins which belong to the ATP-binding cassette superfamily are present in a majority of human tumors and are an important final cause of therapeutic failure. Therefore, some compounds which inhibit the function of the MDR-efflux proteins may improve the cytotoxic action in cancer chemotherapy. The mechanism of action was believed to be a competition between their resistance modifiers and the cytotoxic agents for the same binding site of MDR P-glycoprotein (P-gp) due to a complementarity with a hypothetic receptor site with unknown structure. In the absence of the crystal structures of the P-gp, a receptor fitting was not available. Therefore, we tried to indirectly define the receptor structure or mapping of human MDR1-encoded P-gp in the presence of the structurally unrelated carotenoids, flavonoids, isoflavones and terpenoids.

Synthesis of heterocycle-annulated azulenequinone derivatives

Treatment of 2-methoxyazulene (2) with 4.2 equiv. of bromine in aqueous THF at 0°C for 1 h afforded 3-bromo-2-methoxy-1,5- (la) and -1,7-azulenequinone (1b) in a 16:1 ratio. Reaction of la with o-aminobenzenethiols gave 12H-azuleno[1,2-b]benzo[e][1,4]thiazine-7,11-dione derivatives (6a,b).

Theoretical Studies on Phenothiazines, Benzo(a)phenothiazines, and Benz(c)acridines

Quantitative structure–activity relationship (QSAR) analysis for minimum inhibitory concentration (MIC) of phenothiazines and benzo[a]phenothiazines was investigated based on the theoretical calculations. Four different dipole moments (μ G, μ ESP−G, μ W, and μ ESP−W) and heats of formation (ΔH f) of the phenothiazines [1–20], benzo [a]phenothiazines [21–29], and benz[c]acridines [30–41] were separately calculated in the gas-phase and the water-solution by the conductor-like screening model/parametric method 3 (COSMO/PM3) technique. The MIC values of phenothiazines [1–20] were well correlated to ΔΔH f, HOMO energy and μ G. QSAR may be applicable to predict the MIC of phenothiazines.