Aclacinomycin X, a Novel Anthracycline Antibiotic Produced by<i>Streptomyces galilaeus</i>ATCC 31133

Kim, Hang Sub; Kim, Young Ho; Yoo, Ook Joon; Lee, Jun Young

doi:10.1271/bbb.60.906

Cited by 16 publications

(10 citation statements)

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“…An in vitro cytotoxicity study with human cancer cell lines has shown ID-6105 has potent activity against MOLT-4 leukemia cells and SK-MEL-2 melanoma cells (Hong et al, 1994;Kim et al, 1996a;Kim et al, 1996b). Our preliminary studies, in which we used several human cancer cell lines including MDR cell lines, also showed that ID-6105 was more cytotoxic than Dox (unpublished data) and induced cell apoptosis.…”

Section: Introductionmentioning

confidence: 69%

“…ID-6105 is a new aklacinomycin analog isolated from the culture of Streptomyces galilaeus ATCC31133 cells that have been transformed with the aklavinone 11-hydroxylase gene (dnrF) (Hong et al, 1994;Kim et al, 1996a;Kim et al, 1996b). It has potent cytotoxic activities against human tumor cell lines (Kim et al, 1996a;Kim et al, 1996b).…”

Section: Discussionmentioning

confidence: 99%

“…It has potent cytotoxic activities against human tumor cell lines (Kim et al, 1996a;Kim et al, 1996b). In the present study, we investigated the effects of ID-6105 on epithelial ovarian cancer, which arises from transformed epithelial cells due to the activation of protooncogenes and the inactivation of tumor suppressor genes (Park et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…This detrimental side effect has led to an intensive search for new anthracycline family members either by screening blocked mutants (Johdo et al, 1991;Yoshimoto et al, 1986;Nakagawa et al, 1986) or by a hybrid biosynthetic approach (Hwang et al, 1995;Niemi et al, 1995). In the course of studying the biosynthesis, a new anthracycline antibiotic, designated 11-hydroxyaclacinomycin X (ID-6105), was isolated from the culture broth of Streptomyces galilaeus ATCC31133 Correspondence to: Youn Bok Chung, College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763, Korea Tel: 82-43-261-2824, Fax: 82-43-274-0752 E-mail: chungyb@chungbuk.ac.kr (Hong et al, 1994;Kim et al, 1996a;Kim et al, 1996b) and identified as 7-(O-rhodosaminyl-deoxyfucosyl-rednosyl)-aklavinone ( Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

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Extensive intracellular accumulation of ID-6105, a novel anthracycline, in SK-OV-3 ovarian cancer cells

et al. 2008

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We investigated the anticancer activity of 11-hydroxyaclacinomycin X (ID-6105), a novel anthracycline, on weakly doxorubicin (Dox)-resistant SK-OV-3 ovarian cancer cells, and elucidated the relationship between its anticancer activity and accumulation in cells compared with those of Dox. Accumulation of ID-6105 in the cells was time-and concentration-dependent, a result of drug-induced cytotoxicity in the cells. SK-OV-3 cells were preloaded with ID-6105 or Dox for 12 h at concentrations ranging from 100 to 2000 nM and then incubated with drug-free medium for 0-48 h. Cell viability was measured using a proliferation-based assay (XTT assay). The inhibitory effects of ID-6105 on cell viability were more pronounced than those of Dox. The IC(50) values of ID-6105 after 24-and 48-h incubation with drug-free medium were 1.58 and 0.084 microM, while those of Dox were 2 and 0.334 microM, respectively. To investigate the relationship between the intracellular levels and the cytotoxic effects of the drugs, we preloaded SKOV-3 cells with ID-6105 or Dox (100-2000 nM) for 12 h and then measured the intracellular levels of drugs by HPLC in drug-free medium for 0-48 h. After preloading the drugs, the intracellular concentrations of ID-6105 at time 0 were 1.3-, 1.8-, and 1.4-fold larger than those of Dox at initial concentrations of 500, 1000, and 2000 nM, respectively. The extent of ID-6105 accumulation in the cells was more pronounced than that of Dox. These findings suggest that ID-6105 effluxed less from the cells than Dox, resulting in its extensive cytotoxicity compared with that of Dox. These results show that accumulation of ID-6105 within tumor cells may be important for the inhibitory effects of this drug in cancer cells. ID-6105 has an antiproliferative effect on SK-OV-3 cells that is due to its cytotoxicity. This effect is more pronounced than that of Dox, and may be attributed to extensive accumulation of ID-6105 in the cells.

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Section: Introductionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Extensive intracellular accumulation of ID-6105, a novel anthracycline, in SK-OV-3 ovarian cancer cells

et al. 2008

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“…이러한 전신 부작용을 줄이기 위해 새로운 anthracycline 계열 항생물질들이 개발되고 있다 [3][4][5][6][7]. 새로운 anthracycline 계열 항생물질 개발을 위한 연구의 하나로 11-hydroxyaclacinomycin X (HAMX)가 생합성을 통해 개발되어 보고되었다 [8][9][10]. HAMX는 Streptomyces galilaeus ATCC 3113 (pMC213) 균주로부터 생합성되어 얻은 물 질로서 7-(O-rhodosaminly-deoxyfucosylrednosyl)-aklavinone이다( Fig.…”

Section: Introductionunclassified

Interspecies pharmacokinetic scaling of 11-hydroxyaclanomycin X based on animal data

신대환¹,

이소영²,

Woo³

et al. 2017

J Biomed Transl Res

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The pharmacokinetics of 11-Hydroxyaclacinomycin X (HAMX), a novel anthracycline, were investigated after intravenous bolus administration in mice, rats, rabbits and dogs. Based on animal data, we predicted the following human pharmacokinetic parameters using allometric scaling: 24.1 and 6.99 mL/min/kg for total body clearance (CLt) using simple and maximum lifespan potential (MLP)-corrected allometry, respectively; 5.72 L/kg for steady-state volume of distribution (Vdss). The corresponding allometric equation were CLt = 45.896W 0.8452 , CLt × MLP = 31.175W 1.1405 and Vdss = 10140x 0.8653. These allometric equations were extrapolated to predict CLt and Vdss in human based on 70 kg body weight. We also predicted human parameters using species-invariant time transformations (equivalent time, kallynochrons, apolysichrons and dienetichrons). The values of Vdss (15.4-19.4 L/kg) obtained using invariant time transformations were larger than those obtained using simple allometry. However, the lowest CLt (17.0 mL/min/kg) derived using dienetichrons was comparable to that obtained using simple allometry. The results of this study also indicated that the predicted human CLt generated using MLP-corrected allometry can be used for the selection of a safe dose for studies in healthy adult human volunteers. These results suggest that such approaches may be useful in designing pharmacokinetic studies for novel anthracyclines. The preliminary parameter values may be useful in designing early pharmacokinetic studies of HAMX in humans. The results could also be used to determine the safe dose for the therapeutics in various animals.

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Oxidative Ring‐Expansion of a Chitin‐Derived Platform Enables Access to Unexplored 2‐Amino Sugar Chemical Space

et al. 2019

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The chitin obtained from crustacean shell waste and other renewable resources may be used as a primary feedstock in the biorefineries of the future. Accordingly, the incorporation of chitin‐derived building blocks into new synthesis processes will accentuate the utility of this biopolymer, particularly in the production of bio‐based small molecules that contain one or more nitrogen atoms. Herein we report that enantioenriched 2‐amino sugars are readily accessible from the chitin‐derived platform 3‐acetamido‐5‐acetylfuran (3A5AF). Subjecting 3A5AF to a Noyori reduction–Achmatowicz rearrangement sequence gave N‐acetyl‐l‐rednose (RedNAc) in excellent yield and enantiopurity. Acetamide hydrolysis gave l‐rednose, a rare 2‐amino sugar found in natural anthracycline and angucycline antibiotics. RedNAc was subsequently shown to be a versatile platform from which a variety of stereochemically pure 2‐amino sugars are readily attainable. The synthesis of chiral, bio‐based N‐compounds from chitin emphasises the rapidly expanding utility of this biopolymer as a viable platform for fine chemical production.

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Aclacinomycin X, a Novel Anthracycline Antibiotic Produced byStreptomyces galilaeusATCC 31133

Cited by 16 publications

References 1 publication

Extensive intracellular accumulation of ID-6105, a novel anthracycline, in SK-OV-3 ovarian cancer cells

Extensive intracellular accumulation of ID-6105, a novel anthracycline, in SK-OV-3 ovarian cancer cells

Interspecies pharmacokinetic scaling of 11-hydroxyaclanomycin X based on animal data

Oxidative Ring‐Expansion of a Chitin‐Derived Platform Enables Access to Unexplored 2‐Amino Sugar Chemical Space

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