• YAKHAK HOEJI
• /
• v.44 no.2
• /
• pp.141-148
• /
• 2000

A new synthetic method of 6-(1-oxyalkyl)-5,8-dimethoxy-1,4-naphthoquinones was developed, 2-formyl-1,4,5,8-tetramethoxynaphthalene was oxidized to form 6-formyl-5,8-dimethoxy-1,4-naphthoquinone(DMNQ). This was selectively reduced and benzylated to produce 6-formyl-5,8-dimethoxy-1,4-dibenzyloxynaphthalene, to which various alkylmagnesium halide were added, followed by debenzylation and oxidation in sequence, yielding 6-(1-hydroxyalkyl)-DMNQ derivatives. 6-(1-hydroxyalkyl)-5,8-diethoxy-1,4-naphthalene (DENQ) derivatives were synthesized by similar procedure. 1'-OH of the naphthoquinone derivatives was acylated with various alkanoic acids to give 6-(1-acyloxyalkyl)-DMNQ or DENQ derivatives. TOPO-I inhibitory activity and cytotoxicity of DENQs were less potent than that of DMNQs. Among the DMNQ and DENQ analogues, the ones with alkyl group being heptyl were most potent in TOPO-I inhibition $IC_{50}$/; 30.1, 36.4 $\mu$M). DUNQ derivatives with a longer side chain exhibited a weaker cytotoxicity. A correlation between size of the alkyl side chain and cytotoxicity was not observed for DENQ derivatives. Acylation of 1'-hydroxyl group, in general, decreased both TOPO-I inhibitory activity and cytotoxicity T/C (%) values of the DENQ derivatives on S-180 intraperitoneal tumor were larger than those of DMNQ derivatives. Among the compounds synthesized,6-(1-hydroxyheptyl)-DENQ and 6-(1-hex-anoyloxyoctyl)-DMNQ showed the highest T/C values of 183% and 182%, respectively.

• Proceedings of the Korean Society of Food Hygiene and Safety Conference
• /
• 2004.05a
• /
• pp.233-233
• /
• 2004

• Bulletin of the Korean Chemical Society
• /
• v.20 no.5
• /
• pp.531-534
• /
• 1999

Irradiation (300 nm UV light) of dibenzoylmethane and 1,4-naphthoquinone in dichloromethane gave 1,5-dike-tone as the major product, along with β-hydroxyketone as the minor product. Anthraquinone and anthrone also added photochemically to dibenzoylmethane to give 1,5-diketones as the major products. In contrast, tetrahalo-1,4-benzoquinones added to dibenzoylmethane to give two types of 1,5-diketones via oxetane and cyclobutane intermediates. Comparison of the potential energy values of the photoproducts reveals that the 1,5-diketones are more stable than the corresponding oxetanes or cyclobutanes due to the ring-strain of the bicyclic compounds.

• Archives of Pharmacal Research
• /
• v.26 no.12
• /
• pp.1047-1054
• /
• 2003

Molecular chaperones have a crucial role in the folding of nascent polypeptides in endoplasmic reticulum. Some of them are known to be sensitive to the modification by electrophilic metabolites of organic pro-toxicants. In order to identify chaperone proteins sensitive to alkyators, ER extract was subjected to alkylation by 4-acetamido-4 -maleimidyl-stilbene-2,2 -disulfonate (AMS), and subsequent SDS-PAGE analyses. Protein spots, with molecular mass of 160, 100, 57 and 36 kDa, were found to be sensitive to AMS alkylation, and one abundant chaperon protein was identified to be protein disulfide isomerase (PDI) in comparison with the purified PDI. To see the reactivity of PDI with cysteine alkylators, the reduced form ($PDI_{red}$) of PDI was incubated with various alkylators containing Michael acceptor structure for 30 min at $38^{\circ}C$ at pH 6.3, and the remaining activity was determined by the insulin reduction assay. Iodoacetamide or N-ethylmaleimide at 0.1 mM remarkably inactivated $PDI_{red}$ with N-ethylmaleimide being more potent than iodoacetamide. A partial inactivation of $PDI_{oxid}$ was expressed by iodoacetamide, but not N-ethylmaleimide (NEM) at pH 6.3. Of Michael acceptor compounds tested, 1,4-benzoquinone ($IC_{50}, 15 \mu$ M) was the most potent, followed by 4-hydroxy-2-nonenal and 1,4-naphthoquinone. In contrast, 1,2-naphthoquinone, devoid of a remarkable inactivation action, was effective to cause the oxidative conversion of $PDI_{red}$ to $PDI_{oxid}$. Thus, the action of Michael acceptor compounds differed greatly depending on their structure. Based on these, it is proposed that POI, one of chaperone proteins in ER, could be susceptible to endogenous or xenobiotic Michael acceptor compounds in vivo system.

• YAKHAK HOEJI
• /
• v.41 no.6
• /
• pp.829-836
• /
• 1997

Studies on the effect of quinones on cardiac function has been conducted with normal hearts. But not with injured hearts, I.e. ischemia/reperfusion-injured heart. Quinone compounds are known to produce oxygen free radicals during metabolism, and for this reason, quinones are implicated in the aggravation of ischemia/reperfusion injury or cardioprotection, as in the case of ischemic preconditioning depending on the experimental conditions. The present study was carried out to examine the effect of 2-chloro-3-(4-cyanophenylamino)-1.4-naphthoquinone (NQ-Y15) on cardiac function of ischemic/reperfused and normal rat hearts. In isolated perfused hearts, various functional parameters such as left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (EDP) and maximum positive and negative dP/dt ($[\pm}dP/dt_{max}$), time to contracture, heart rate (HR) and coronary flow rate (CFR) were measured before and 30 min after dosing and following 25 min ischemia/30min reperfusion. NQ-Y15 increased LVDP, +dP/$d_{max}$and -dP/$dt_{min}$ by 18%. 30%, and 40%, respectively. There were no significant changes in other haemodynamic parameters. After ischemia/reperfusion injury, pretreatment with NQ-Y15 induced a significant decrease in LVDP and $[\pm}dP/dt_{max}$, but an increase in EDP. LDH-release was not significantly increased. These results suggested that NQ-Y15 may augment the ventricular contractility but it makes hearts more vulnerable to ischemia/reperfusion injury.

• Bulletin of the Korean Chemical Society
• /
• v.34 no.9
• /
• pp.2825-2828
• /
• 2013

• Archives of Pharmacal Research
• /
• v.22 no.4
• /
• pp.414-416
• /
• 1999

A shkionin derivative was isolated from the roots of Lithospermum erythrorhizon with silica gel column chromatography and preparative TLC. The structure of the isolated pigment was identified as propionylshikonin by NMR and mass spectrometric analysis. The isolation of propionylshiknin was for the first time in the nature.

• Proceedings of the Korea Environmental Mutagen Society Conference
• /
• 2002.05a
• /
• pp.119-119
• /
• 2002

• Proceedings of the PSK Conference
• /
• 2001.04a
• /
• pp.119.2-119.2
• /
• 2001

• Proceedings of the PSK Conference
• /
• 2003.10b
• /
• pp.185.3-185.3
• /
• 2003

Juglone and naphthazarine derivatives were newly systhesized for the evaluation of antifungal activities. These derivatives were prepared by methylation of juglone and 2, 3-dichloro-5, 8-dihydroxy-l, 4-naphthoquinone, and by regioselective nucleophilic subsitution with arylthiols. All compounds were tested in vitro for their growth inhibitory activities against pathogenic fungi by the standard method. The MIC values were determined by comparison to flucytosine as a standard agent. (omitted)