• Parasites, Hosts and Diseases
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• 제31권1호
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• pp.57-66
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• 1993

향어의 장포자충증을 예방, 치료하기 위한 일환으로 fumagillin의 효과시험을 야외에서 수행하였다. 실험 1(치료)에서는 장포자충증의 종류가 중등도로 형성된 향어 (평균체중 830 발를 3군으로 나누어 가두리에 사육하였다. 하루에 처음 군은 10.62 mg, 두번째 군은 5.3 mg의 fumagillin을 8월 1일부터 한달동안 사료에 혼합하여 투여하였으며 세번째 군은 대조로 하였다. 실험 2(예방)에서는 장포자충중이 초기상태인 향어 (평균체중 484 g를 2군으로 나누어 가두리에 사육하였다. 처음 군에는 하루에 3.95 mg의 fumagillln을 7월 17일부터 45일 동안 역시 사료에 혼합하여 투여하였으며 다음 군은 대조로 하였다. 두 실험에서 향어의 누적 폐사율과 포자의 극사탈출율은 약제농도의 차이에 관계없이 대조군에 비하여 모두 의의있게 감소하였다. 약제에 의한 부작용은 전혀 관찰할 수 없었으며, 특히 실험 2에서 폐사어는 전혀 인정할 수 없었다. 약제 투여후 실험 1의 15일째와 실험 2의 7일째에 대부분 종류의 중앙부에 하나의 만원형 또는 작은 점 비슷한 함몰부가 형성되었으며, 실험 1의 15일째와 실험 2의 17일째에는 관상영양형의 횡단면이 전혀 인정되지 않았다. 실험 2의 24일째와 실험 1의 30일째에 있어서 종류의 조직학적 소견은 치유과정을 취하고 있었으며, 실험 2의 경우 24일이후에는 종류의 크기가 대조에 비하여 모두 현저하게 작았다. 이상의 실험결과로 미루어 보아 장포자충증을 예방, 치료하기 위하여 종류가 형성되기 전인 7월 상순에 체중 500 g 향어에 매일 3.95 mg의 fumagillin을 한달동안 경구투여하는 것이 가장 효과적이라고 하겠다.

• Advances in pediatric surgery
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• 제8권2호
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• pp.101-106
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• 2002

The antiangiogenic effects of novel agent KJ3, Betulinic acid, and Fumagillin on the neovascularization were studied by examining ultrastructural alterations in the vasculature of synthetic gelform and mouse neuroblastoma C1300. Small pieces of gelform with 0.4% agar were introduced subcutaneously (s.c.) in 7 week old male CH3/HeJ mice. After the $LD_{50}s$ were determined by FACS analysis, a third of $LD_{50}$ of three drugs were injected either locally or intraperitoneally every other day for 14 days. A/J mice were inoculated s.c. with the C1300 neuroblastoma cell line, then either saline or three drugs were injected in the same manner. The antiangiogenic effects of three drugs were studied by measuring the histologic changes in tumors, and immunostaining for CD34, VIII/vWF, CD105, and thymidine phosphorylase. In the drug treated groups, the number of vessels in gelform experiments and C1300 neuroblastoma experiments were lower than the corresponding values in the control. The histologic findings were significantly different in drug treated groups on day 7, but these were not significant on day 14. These results imply that antiangiogenic agents were effective when the tumor burden is minimal.

• Archives of Pharmacal Research
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• 제28권2호
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• pp.129-141
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• 2005

(-)-Fumagillol (1), a hydrolysis product of fumagillin, has been synthesized by several group from commercially available 1,2:5,6-di-O-isopropylidene-${\alpha}$-D-allofuranose in a highly stereoselective manner. Chiral centers on C5 and C6 came from D-allofuranose and the asymmetric center on C4 was accomplished by 1,3-chirality transfer using the Claisen rearrangement on a chiral allyl alcohol. Chirality, which is necessary on an epoxide consisting of the spiro-ring system, was diastereoselectively constructed by the well-known reaction, intramolecular ester enolate alkylation (IEEA), which showed that this reaction can be applied to the alpha-alkoxy ester system. The epoxide on the side chain was regioselectively introduced by the difference between the number of substituents on the vinyl groups. This accomplishment proved that IEEA can be a useful tool for the synthesis of complex molecules.

• 대한약학회:학술대회논문집
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• 대한약학회 2001년도 Proceedings of International Convention of the Pharmaceutical Society of Korea
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• pp.306.1-306.1
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• 2001

• Archives of Pharmacal Research
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• 제27권2호
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• pp.265-272
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• 2004

The pharmacokinetics of CKD-732 (6-0-4-[dimethyl-aminoethoxy)cinnamoyl]-fumagillolㆍhemioxalate) was investigated in male SD rats and beagle dogs after bolus intravenous administration. The parent compound and metabolites obtained from in vitro and in vivo samples were determined by LC/MS. The main metabolite was isolated and identified as an N-oxide form of CKD-732 by NMR and LC/MS/MS. CKD-732 was metabolized into either M11 or others by rapid hydroxylation, demethylation, and hydrolysis. The blood level following the intravenous route declined in first-order kinetics with $T_{1}$2/$\beta$ values of 0.72-0.78 h for CKD-732 and 0.92-1.09 h for M11 in rats at a dose of 7.5-30 mg/kg. In dogs, $T_{1}$2/$\beta$ values of CKD-732 and M11 were 1.54 and 1.79 h, respectively. Moreover, AUC values increased dose dependently for CKD-732 and M11 in rats and dogs. The CLtot and Vdss did not change significantly with increasing dose, indicating linear pharmacokinetic patterns. The excretion patterns through the urine, bile, and feces were also examined in the animals. The total amount excreted in urine, bile, and feces was 2.13% for CKD-732 and 1.29% for M11 in rats, and 1.58% for CKD-732 and 2.28% for M11 in dogs.

• Journal of Microbiology and Biotechnology
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• 제23권6호
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• pp.766-770
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• 2013

Several upstream activators required for proper activation of brlA are involved in the development, vegetative growth, toxin production, and pathogenesis of Aspergillus fumigatus. In this study, we characterized the roles of two upstream developmental regulators, A. fumigatus flbB (AfuflbB) and flbE (AfuflbE), in toxin production and virulence. The deletion of AfuflbB and AfuflbE resulted in reduction of the expression of AfulaeA. Moreover, only about 8% to 10% of fumagillin was produced in the two mutants compared with that of wild type, and ${\Delta}AfuflbB$ strain produced 85% of gliotoxin compared with wild type, whereas none was produced by ${\Delta}AfuflbB$. Flow-cytometric analysis revealed decreased necrotic and apoptotic polymorphonuclear leukocytes cell death after exposure to supernatants from ${\Delta}AfuflbB$ and ${\Delta}AfuflbB$ strains compared with the wild type. These results indicate that FlbB and FlbE are necessary for the proper laeA expression, toxin production, and virulence of A. fumigatus.