• Biomolecules & Therapeutics
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• 제28권4호
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• pp.370-379
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• 2020

Econazole, a potent broad-spectrum antifungal agent and a Ca²⁺ channel antagonist, induces cytotoxicity in leukemia cells and is used for the treatment of skin infections. However, little is known about its cytotoxic effects on solid tumor cells. Here, we investigated the molecular mechanism underlying econazole-induced toxicity in vitro and evaluated its regulatory effect on the metastasis of gastric cancer cells. Using the gastric cancer cell lines AGS and SNU1 expressing wild-type p53 we demonstrated that econazole could significantly reduce cell viability and colony-forming (tumorigenesis) ability. Econazole induced G0/G1 phase arrest, promoted apoptosis, and effectively blocked proliferation- and survival-related signal transduction pathways in gastric cancer cells. In addition, econazole inhibited the secretion of matrix metalloproteinase- 2 (MMP-2) and MMP-9, which degrade the extracellular matrix and basement membrane. Econazole also effectively inhibited the metastasis of gastric cancer cells, as confirmed from cell invasion and wound healing assays. The protein level of p53 was significantly elevated after econazole treatment of AGS and SNU1 cells. However, apoptosis was blocked in econazole-treated cells exposed to a p53-specific small-interfering RNA to eliminate p53 expression. These results provide evidence that econazole could be repurposed to induce gastric cancer cell death and inhibit cancer invasion.

• 한국결정학회지
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• 제1권1호
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• pp.14-18
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• 1990

Econazole nitrate, 1-{2-[(4-chlorophenyl)methoxy]-2-(2,4-dichlorophenyl) ethy1}-1H-imidazole mono-nitrate, C18 H16 CI13 N3 O4의 단위세포 상수는 a=19.337(4) A, b=15.191(5) A c=7.601(3)A, β=91.72(2)μ V=2000.0A3 Do=1.49g/ml Dm=1.47g/ml, M=4.31cm-1 F(000)=912.0, 2T=298K,공간군은 P2₁/C이고 단사 정계이며 Z=4이다. λ=(Mo-Ka)=0.7107 A을 사용한 1330개의 Intensity data에 대해 최종 R값은 0.06이다. Econazole nitrate의 각 세 ring은 각각 평면이며 B,A,C ring순서로 층계를 이루고 있다. 반면에 Econazole의 A와 C ring은 거의 같은 평면에 누워 있으나 B ring 은 거의 같은 평면이며 B,A,C ring순서로 층계를 이루고 있다.반면에 Econazole의 A와 C ring은 거의 같은 평면에 누워있으나 B ring과는 약 60˚의 평면각을 이루고 있다. Nitrate의 O(*3)와 Imidaze의 N(2) 사이의 수소결합은 Econazole slt의 안정화에 기여한다.

• 대한수의학회지
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• 제29권1호
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• pp.69-73
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• 1989

준임상형 유방염 이환 젖소의 유즙과 유두컵으로부터 분리된 Candida속 균의 8종 항진균성약제에 대한 감수성을 조사하였던 결과는 다음과 같다. 총 53주의 Candida속균 중 98.2%, 94.4%, 84.8%의 균주가 각각 clotrimazole, econazole, miconazole의 농도 $25{\mu}g/ml$이하에서 발육이 억제됨으로서, 이들 약제의 항균력이 타 약제에 비하여 우수하였다. 균종별로 보면 C albicans는 clotrimazole에 대한 감수성이 가장 높았으며, 기타 비교적 감수성이 높았던 약제는 5-fluorocytosine, econazole, miconazole의 순이었다. C pseudotropicalis와 C guilliermondii는 haloprogin, clotrimazole, miconazole, econazole, 5-fluorocytosine등에 높은 감수성을 나타내었으며, haloprogin의 평균 MIC가 $0.17{\sim}0.19{\mu}g/ml$로 가장 우수하였다. C krusei는 cycloheximide에 대한 감수성이 가장 높았으며, 그의 비교적 감수성이 높았던 약제는 clotrimazole, haloprogin, miconazole, econazole의 순이었다. 한편 C parapsilosis는 econazole, cycloheximide, clotrimazole등에 다소 감수성을 나타내었으나, 이들 약제의 MIC는 econazole(기하평균 MIC $7.26{\mu}g/ml$)을 제외하고는 타균종에서 보다 현저히 낮았다. 또한 C tropicalis는 전 공시약제에 대하여 감수성이 낮은 경향이었다.

• 약학회지
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• 제45권3호
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• pp.282-286
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• 2001

To investigate the different mechanism between ATP and compound 48/80 (C$_{48}$80/)-induced histamine release, we observed effects of calcium antagonists in histamine release of rat peritoneal mast cells. Verapamil and diltiazem (voltage-dependent calcium channel blocker) and TMB-8 (a blocker of intracellular calcium release) significantly inhibited ATP-induced histamine release, but did not inhibit $C_{48}$80/-induced histamine release. Econazole (a blocker of receptor-operated calcium channel) dose-dependently inhibited both ATP and $C_{48}$80/-induced histamine release, but inhibitory effect of econazole in ATP-induced histamine release was more potent than that in $C_{48}$80/-induced histamine. EGTA dose-dependently inhibited ATP and $C_{48}$80/-induced histamine release, but $C_{48}$80/-induced histamine release was slightly inhibited by high concentrations (>2 mM) of EGTA. These results suggest that ATP-induced histamine release is related to broth intracellular calcium release and extracellular calcium influx via voltage-dependent calcium channel and receptor-operated calcium channel. $C_{48}$80/-induced histamine release is related to extracellular calcium influx, especially by receptor-operated calcium channel rather than voltage-dependent calcium channel.

• Journal of Pharmaceutical Investigation
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• 제19권3호
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• pp.145-154
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• 1989

Methyl methacrylate-butyl methacrylate copolymer (MMBM)-povidone (PVP) films were investigated as a potential topical drug delivery system for the controlled release of econazole nitrate as a model drug. The effect of changes in film composition, drug concentration, film thickness, pH and temperature of release medium on the in vitro release of econazole nitrate were studied. The release rate constant was found to be increased with increasing povidone content in dry films. Drug release followed zero-order kinetics in the initial stage and then release rate increased gradually with time, espicially in the films having larger proportions of PVP. The release rate was found to be dependent on drug content, film thickness, the pH and temperature of release medium. Antimicrobial test showed that microbial growth was inhibited markedly with increasing proportions of PVP in films. Also drug content and film thickness affected the antimicrobial activity.

• 한국균학회지
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• 제4권1호
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• pp.53-58
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• 1976

This study was undertaken to investigate the direct effect of three different kinds of steroid to Trichophyton(T.) mentagrophytes growth in vitro. A loopful of T. mentagrophytes was inoculated into Sabouraud's media and Sabouraud's media containing various concentrations of dexamethasone (0.04%-0.00004%) prednisolone (0.25%-0.00025%), triamcinolone acetonide (0.2%-0.0002%), Sabouraud's media containing imidazole nitrate (econasole nitrate) 10 micro gm. per cc. of media, and Sabouraud's media containing econazole nitrate $10{\mu}g$ per cc. of media of various dexamethasone concentrations (0.04%-0.00004%). After inoculation they were left for two weeks at room temparature and the colony diameter were compared between Sabouraud's media and Sabouraud's media containing various concentrations, of three different steroids, Sabouraud's media containing econazole nitrate and Sabouraud's media containing econazole nitrate of various dexamethasone concentrations. For complementary study, hanging slide culture were done between Sabouraud's media and Sabouraud's media containing various dexamethasone concentrations to compare the degree of branching of hyphae and sporulation serially. The study results were as follows: 1. There is no significant difference in growth rate of T. mentcgrophytes between Sabouraud's media and Sabouraud's media containing various concentrations of three different steroids. 2. There is no significant difference in growth rate of T. metagrophytes between Sabouraud's media containing econazole nitrate 10 micro gm per cc. of media and Sabouraud's media containing econazole nitrate 10 micro gm per cc. of media of various dexamethasone concentrations. 3. In hanging slide culture, there is no significant difference in branching of hyphae and sporulation between Sabouraud's media and Sabouraud's media containing various dexamethasone concentrations.

• 약학회지
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• 제43권2호
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• pp.221-227
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• 1999

The fungistatic and fungicidal activities of amphotericin B, fluconazole, miconazole, econazole, and 5-fluorocytosine against Saccharomyces cerevisiae were estimated in the presence of 1/2 minimum inhibitory concentration (MIC) and 1/2 minimum fungicidal concentration (MFC) of polygodial, respectively. Among them, the antifungal activities of miconazoles by polygodial was still shown against several yeast-like fungi including Candida albicans, Candida utilis, Cryptococcus neoformans, except for Candida krusei. The combination of polygodial with imidazole drugs against Saccharomyces cerevisiae was further examined using the macrobroth dilution checkerboard method. The fractional inhibitory concentration (FIC) and the fractional fungicidal concentration (FFC) index between polygodial and miconazole were 0.16 and 0.19, while the combination of polygodial with econazole exhibited the FIC index of 0.19 and the FFC of 0.25, respectively. These results suggest that polygodial and the imidazoles on the fungistatic and fungicidal action are highly synergistic.

• 약학회지
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• 제43권5호
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• pp.659-664
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• 1999

To investigate the difference of contractile mechanism between KCI and phenylephrine-induced contraction, we observed effects of $Ca^{2+}$ antagonists and protein kinase inhibitors on aorta contraction of rats. Verapamil dose-dependently inhibited the contraction induced by KCI and phenylephrine, the inhibitory effect of verapamil was more potent in KCI-induced contraction than phenylephrine-induced contraction. Econazole and TMB-8 significantly inhibited CKI-induced contraction but did not inhibit phenylephrine-induced contraction. Staurosporine dose-dependently inhibited both KCI and phenylephrine-induced contraction. Genistein and calmodulin antagonists (W-7 and trifluoperazine) also inhibited both contraction in a dose dependent manner. However, the inhibitory effects of genistein and calmodulin antagonists were more potent in phenylephrine-induced contraction than KCI-induced contraction. These results suggest that involvements of $Ca^{2+}$ channel and protein kinase in rat aorta contraction were dependent on agonist causing aorta smooth muscle contraction.

• Animal cells and systems
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• 제10권4호
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• pp.203-209
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• 2006

Azoles are widely used antifungal agents, which inhibit the biosynthesis of fungal cell-membrane ergosterol. In this study, using an amphibian follicle culture system, the effects of azoles on follicular steroidogenesis in frogs were examined. Itraconazole (ICZ), clotrimazole (CTZ) and ketoconazole (KCZ) suppressed pregnenolone ($P_5$) production by the follicles ($ED_{50};\;0.04_{\mu}M,\;0.33_{\mu} M,\;and\;0.91_{\mu}M$, respectively) in response to frog pituitary homogenates (FPH). However, fluconazole (FCZ), miconazole (MCZ) and econazole (ECZ) were not effective in the suppression of $P_5$ production. Not all the azoles examined suppressed the conversion of exogenous $P_5$ to progesterone ($P_4$) (by $3{\beta}$- HSD) or $P_4$ to $17{\alpha}$-hydroxyprogesterone ($17{\alpha}$-OHP) (by $17{\alpha}$-hydroxylase), or androstenedione (AD) to testosterone (T) (by $17{\beta}$-HSD). In contrast, CTZ, MCZ and ECZ in medium partially suppressed the conversion of $17{\alpha}$-OHP to AD (by C17-20 lyase) ($ED_{50};\;0.25{\mu} M,\;4.5{\mu}M,\;and\;0.7{mu}M$, respectively) and CTZ, KCZ, ECZ and MCZ strongly suppressed the conversion of exogenous T to estradiol ($E_2$) (by aromatase) ($ED_{50};\;0.02{\mu}M,\;8{\mu}M,\;0.07{\mu}M,\;0.8{\mu}M$, respectively). These results demonstrated that some azole agents strongly suppress amphibian follicular steroidogenesis and particularly, P450scc and aromatase are more sensitive to azoles than other steroidogenic enzymes.

• 대한수의학회지
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• 제39권3호
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• pp.560-565
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• 1999

The present work was conducted to investigate the drug susceptibility of microorganisms isolated from canine external ear canals. Antifungal susceptibility test of M pachydermatis (17 strains) was perfomed by agar dilution method, using 11 antifungal drugs including amphotericin B(A), nystatin(N), pimaricin(P), griseofulvin(G), bifonazole(B), clotrimazole(C), miconazole(M), econazole(E), ketoconazole(K), tolnaftate(T), 5-fluorocytosine(F). All isolates were highly sensitive to K, M, T(geometric mean MIC ; GM $MIC{\leq}0.16{\mu}g/ml$) but they weren't sensitive to P, F and G(GM $MIC{\geq}92.37{\mu}g/ml{\sim}{\geq}128{\mu}g/ml$). Antibacterial susceptibility test against 119 isolates of bacteria was performed by agar dilution method, using 9 antibacterial drugs including erythromycin(ET), chloramphenicol(CP), gentamycin(G), vancomycin(V), ampicillin(AP), amoxacillin(AX), chlortetracycline(CT), ciprofloxacin(CF), enrofloxacin(EF). All isolates of Staphylococcus spp(101 strains) were highly sensitive to EF, CF, G(GM MIC $0.33{\sim}1.47{\mu}g/ml$). In other gram positive cocci(4 strains), they were highly sensitive to EF, CF, V(GM MIC $1{\sim}4.76{\mu}g/ml$) and CT(GM MIC 1 UFL unit/ml). In gram positive rods(13 strains), they were highly sensitive to EF, CF, G(GM $MIC{\leq}0.19{\sim}1{\mu}g/ml$). In Pseudomonas aeruginosa(1 strain), it was highly sensitive to AX, EF, ET, CF(GM MIC $0.06{\sim}1{\mu}g/ml$) and CT(GM MIC 1 UFL unit/ml). All isolates weren't sensitive to AP(GM MIC 16~>$32{\mu}g/ml$).