• Bulletin of the Korean Chemical Society
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• 제31권1호
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• pp.69-74
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• 2010

The new idarubicin analogues (12 and 13) with a glucose or galactoseas as a glycone were synthesized from daunomycin (2). (+)-4-Demethoxydaunomycinone (6) obtained from reaction of 2 with $AlCl_3$ was converted to 4-trifluoromethanesulfonyl daunomycinone (7) through reaction with trifluoromethanesulfonic anhydride. The treatment of 7 with 1,1-bis-(diphenylphospino)ferrocene/$Pd(OAc)_2$ in triethylamine/formic acid/dioxane provided the idarubicinone (5b). Glycosylation of 7-hydroxy group of 5b with two kinds of tetraacetyl pyranosyl halide (8 and 9) by a modified Koenigs-Knorr procedure and then deacetylation using aqueous 0.1 N LiOH solution and amberlite cationic resin gave the objective materials. The in vitro MTT assay of the analogues (12b and 13a) in comparison with idarubicin (5a) on peripheral blood human promyelocytic-leukemia cell line and human breast cancer cell line were also described.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.212-213
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• 2002

Using the isolated perfused rat heart this study investigated 1) the cardiac uptake of idarubicin (IDA), 2) the role of P-glycoprotein (P-gp) in the uptake process, 3) the formation of IDOL from IDA in the heart, and 4) the effect of P-gp inhibitors (verapamil, amiodarone, PSC 833), doxorubicin, hypothermia, xanthine derivatives (caffeine, theophylline) and metabolism inhibitors (rutin, phenobarbital) on the pharmacokinetics and pharmacodynamics of IDA using a mathematical modeling approach. A minimal model was constructed; the differential equations were numerically solved and fitted to the data using the ADAPT II-software package using maximum likelihood estimation assuming that the measurement error has a standard deviation which is a linear function of the measured quantity［1］. (omitted)

• Bulletin of the Korean Chemical Society
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• 제21권8호
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• pp.774-778
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• 2000

A convenient total synthesis of a new 7-deoxyidarubicinone ivative21,the aglycon of the anticancer anti-biotic idarubicin analogue,is described.Keyfeatures of the synthesis are the Friedel-Crafts acylation and the functionalization of an A-ring si de chain. A synthon 14 for the A and B rings was prepared from intermediate 6 in five steps.

• 분석과학
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• 제20권4호
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• pp.308-314
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• 2007

방사흐름 전지를 연결한 고성능 액체 크로마토그래프를 사용하여 독소루비신, 에피루비신, 노갈라마이신, 다우노루비신 및 아이다루비신을 동시에 정량 할 수 있는 역상 크로마토그래피법을 개발하였다. 안트라사이클린계 항생제들은 이동상 용매 중에서 은/염화은 (0.01 M NaCl) 기준전극에 대하여 확산 전류를 나타내는 -0.74 V에서 검출되었다. 부피 흐름속도 ($V_f$)를 1.0 mL/min로 고정하였을 때 독소루비신, 에피루비신, 다우노루비신 및 아이다루비신은 각각 6.4 분, 7.4분, 12.7분 및 18.4분의 머무름 시간 ($t_r$)에서 나타났으며, $V_f$ 0.6 mL/min 에서는 독소루비신, 에피루비신, 노갈라마이신, 다우노루비신 및 아이다루비신의 $t_r$은 각각 9.9분, 11.5분, 13.5분, 19.6분 및 28.7분에서 나타났다. 주입된 각각의 안트라사이클린계 항생제의 농도 ($2.40{\times}10^{-7}M{\sim}1.42{\times}10^{-5}M$)에 대하여 봉우리 면적 (전하)를 도시하였을 때 상관계수의 제곱 ($R^2$)은 0.999 이상으로 직선 성이 우수하였다. 다섯 가지 안트라사이클린계 항생제의 검출한계는 $1.0{\times}10^{-8}M{\sim}1.5{\times}10^{-7}M$이었으며 정밀도는 $0.7{\mu}M$ 이하의 농도를 제외하고는 상대 표준편차3%($1.00{\times}10^{-6}M{\sim}1.42{\times}10^{-5}M$) 미만이었다. 사람의 혈청 중에 포함된 $1.00{\times}10^{-5}M$ 에피루비신, $0.48{\times}10^{-5}M$ 노갈라마이신 및 $1.52{\times}10^{-5}M$ 다우노루비신을 $C_{18}$ 카트리지로 고상 추출하였을 때 회수율은 각각 97%, 100% 및 90% 이었다.

• Oncology Letters
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• 제42권5호
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• pp.2149-2158
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• 2019

Primary refractory acute myeloid leukemia (AML) and early recurrence of leukemic cells are among the most difficult hurdles to overcome in the treatment of AML. Moreover, uncertainties surrounding the molecular mechanism underlying refractory AML pose a challenge when it comes to developing novel therapeutic drugs. However, accumulating evidence suggests a contribution of phosphatase and tensin homolog (PTEN)/protein kinase B (AKT) signaling to the development of refractory AML. To assess PTEN/AKT signaling in AML, two types of AML cell lines were evaluated, namely control HL60 cells and KG1α cells, a refractory AML cell line that is resistant to idarubicin and cytarabine (AraC) treatment. Changes in the expression level of glycolysis- and mitochondrial oxidative phosphorylation-related genes and proteins were evaluated by reverse transcription-quantitative polymerase chain reaction and western blot analyses, respectively. The mitochondrial oxygen consumption and extracellular acidification rates were measured using an XF24 analyzer. CCK8 assay and Annexin V/PI staining were used to analyze cell viability and cellular apoptosis, respectively. The PTEN protein was found to be depleted, whereas AKT phosphorylation levels were elevated in KG1α cells compared with HL60 cells. These changes were associated with increased expression of glucose transporter 1 and hexokinase 2, and increased lactate production. AKT inhibition decreased the proliferation of KG1α cells and decreased extracellular acidification without affecting HL60 cells. Notably, AKT inhibition increased the susceptibility of KG1α cells to chemotherapy with idarubicin and AraC. Taken together, the findings of the present study indicate that activation of AKT by PTEN deficiency sustains the refractory AML status through enhancement of glycolysis and mitochondrial respiration, effects that may be rescued by inhibiting AKT activity.