57576-44-0 Usage
Originator
Aclacinon ,Yamanouchi ,Japan ,1981
Uses
Different sources of media describe the Uses of 57576-44-0 differently. You can refer to the following data:
1. Aclarubicin is an anthracycline antibiotic. It is used in the treatment of cancer.
2. Antineoplastic.
Definition
ChEBI: An anthracycline antibiotic that is produced by Streptomyces galilaeus and also has potent antineoplastic activity.
Manufacturing Process
100 ml of this medium was sterilized at 120°C for 15 min in a 500 ml
Sakaguchi-shaking flask which was inoculated from an agar slant culture of
Streptomyces galilaeus MA144-M1 by platinum loop. Incubation proceeded for
48 hr at 28°C on a reciprocal shaker. 10 L of the previously sterilized medium
in a 20 L stainless steel jar fermenter were aseptically inoculated with 200 ml
of the above seed cultures. Fermentation was carried out at 28°C for 32 hours
with agitation (240 rpm) and aeration (5 L/min). The cultured broth obtained
was adjusted to pH 4.5, mixed with an adsorbent siliceous earth material and
filtered from the mycelium. The filtrate and cake obtained thereby were
extracted separately. The cake was suspended in acetone (3 L/kg wet cake),
stirred for 2 hr and filtered, and the cake was further extracted with acetone
once again. The extracts thus obtained were evaporated to one-tenth volume
in vacuum. The culture filtrate was adjusted to pH 6.8 and extracted twice
with one-third volume of ethyl acetate, and the ethyl acetate extracts were
concentrated to one-tenth volume in vacuum.
Twenty grams of the resulting oily substances were mixed with 20 grams of
silicic acid (Mallinckrodt Chemical Co.), applied to a column 40 cm in length
and 4.5 cm in diameter filled with silicic acid, and eluted with a benzeneacetone-
methanol mixture. The initial eluate which eluted with a 1:1:0
mixture was discarded and the active fractions eluted with 1:3:0 and 1:3:0.3
mixtures were collected and concentrated to dryness in vacuum. 11.5 g of this
crude substance was then dissolved in a small amount of ethyl acetate and
applied to the same silicic acid column as above. After discarding the initial
eluates by the 1:1 and 2:1 benzene-acetone mixtures, aclacinomycin B
fractions were first eluted with the above mixtures of 1:3 and 1:5 ratio, and
aclacinomycin A fractions were then eluted with the 1:5:0.5 and 1:5:1 benzene-acetone-methanol mixtures. The eluates were dried over anhydrous
sodium sulfate and concentrated to dryness in vacuum. 4.8 g of crude
aclacinomycin A and 3.5 g of aclacinomycin B were obtained as yellow powder.
2.0 g of crude aclacinomycin A obtained as above were dissolved in a small
amount of chloroform, applied to a column 20 cm in length and 20 cm in
diameter filled with 30 g of silicic acid. After eluting off the pigments
containing aglycone and aclacinomycin B and other impurities with chloroform
and 1.5% methanol-containing chloroform, aclacinomycin A fractions were
eluted with 2% methanol-containing chloroform, and concentrated to dryness
in vacuum. 53 mg of yellow powder of aclacinomycin A was obtained. Its
melting point was 129°C to 135°C.
Therapeutic Function
Antitumor, Antibiotic
Biological Activity
aclacinomycin a is a dual inhibitor of topoisomerase i and ii [1]. aclacinomycin a is an anticancer drug which can reduce the tumor with minimal damage to normal cells. aclacinomycin a shows potency against a wide variety of solid tumours and haematological malignancies. in a549, hepg2 and mcf-7 cells, aclacinomycin a shows cytotoxic activity with ic50 values of 0.27μm, 0.32μm and 0.62μm, respectively. aclacinomycin a induces cell apoptosis in these cells and the effects change to be necrosis when the incubation time is prolonged. aclacinomycin a is demonstrated to increase the activity of both caspase-3 and caspase-8, thus inducing the activation of parp. apart from that, as an inhibitor of opoisomerases, aclacinomycin a is found to induce dna damage in v79 and irs-2 cells. aclacinomycin a is used to treat acute leukaemias, lymphomas and other solid tumors through its inhibition of topo ii [1, 2].
Safety Profile
Poison by ingestion,intraperitoneal, subcutaneous, and intravenous routes. Anexperimental teratogen. Other experimental reproductiveeffects. Mutation data reported. An eye and subcutaneousirritant. When heated to decomposition it emits toxicfumes of
Enzyme inhibitor
This non-peptidic aclacinomycin antibiotic (FW = 811.88 g/mol; CAS CAS 57576-44-0; Source: strain of Streptomyces galilaeus), also known as aclarubicin, induces DNA strand scission. Target(s): nitric oxide synthase; RNA biosynthesis; DNA polymerase I; RNA polymerase, Escherichia coli; reverse transcriptase, avian myeloblastosis virus; Na+/K+-exchanging ATPase; Ca2+-transporting ATPase; cyclicnucleotide phosphodiesterase; electron transport and oxidative phosphorylation, mitochondrial; DNA helicase; DNA topoisomerase II; 20S proteasome, chymotrypsin-like activity; DNA topoisomerase I; 3'-5' DNA helicase, Plasmodium falciparum.
references
[1] hajji n, mateos s, pastor n, domínguez i, cortés f. induction of genotoxic and cytotoxic damage by aclarubicin, a dual topoisomerase inhibitor. mutat res. 2005 may 2;583(1):26-35.[2] rogalska a, szwed m, jó wiak z. aclarubicin-induced apoptosis and necrosis in cells derived from human solid tumours. mutat res. 2010 jul 19;700(1-2):1-10.
Check Digit Verification of cas no
The CAS Registry Mumber 57576-44-0 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 5,7,5,7 and 6 respectively; the second part has 2 digits, 4 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 57576-44:
(7*5)+(6*7)+(5*5)+(4*7)+(3*6)+(2*4)+(1*4)=160
160 % 10 = 0
So 57576-44-0 is a valid CAS Registry Number.
InChI:InChI=1/C42H53NO15/c1-8-42(51)17-28(33-22(35(42)41(50)52-7)14-23-34(38(33)49)37(48)32-21(36(23)47)10-9-11-26(32)45)56-30-15-24(43(5)6)39(19(3)54-30)58-31-16-27(46)40(20(4)55-31)57-29-13-12-25(44)18(2)53-29/h9-11,14,18-20,24,27-31,35,39-40,45-46,49,51H,8,12-13,15-17H2,1-7H3/t18-,19-,20-,24-,27-,28-,29-,30-,31-,35-,39+,40+,42+/m0/s1
57576-44-0Relevant articles and documents
New betaclamycin and aclarubicin analogs obtained by prolonged microbial conversion with an aclarubicin-negative mutant
Johdo, Osamu,Yoshioka, Takeo,Naganawa, Hiroshi,Takeuchi, Tomio,Yoshimoto, Akihiro
, p. 669 - 675 (2007/10/03)
Microbial conversion of β-rhodomycinone and aklavinone using an aclarubicin-negative Streptomyces galilaeus mutant afforded new anthracycline antibiotics CG21-C and CG1-C which had a rednosyl-2-deoxyfucosyl-rhodosaminyl trisaccharide residue at C-7 of each added aglycone. They were produced only when a prolonged conversion culture took place. Because the usual conversion products containing a cinerulosyl-2-deoxyfucosyl-rhodosaminyl residue were at first accumulated and then decreased during further cultivation, it was evident that they occurred by the modification of terminal cinerulose. The isolation, purification, and structural determination are described, and cytotoxicity in vitro against cultured L1210 cells and the formation mechanism are discussed.
