Name: Doxorubicin
Brand: BOC Sciences
Rating: 5 (1 reviews)

Synonyms

Daunorubicin Impurity D; Daunorubicin EP Impurity D; (8S,10S)-10-[(3-Aamino-2,3,6-trideoxy-α-L-lyxohexopyranosyl)oxy]-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione; Adriamycin; Doxil; Adriablastin; Doxorubicine; Adriblastina; 14-Hydroxydaunomycin; 14-Hydroxydaunorubicine; Caelyx; Hydroxydaunorubicin; 5,12-Naphthacenedione, 10-((3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl)oxy)-7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, (8S-cis)-; NSC 123127; (1S,3S)-3,5,12-Trihydroxy-3-(hydroxyacetyl)-10-(methyloxy)-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl 3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranoside; Epirubicin EP Impurity C

IUPAC Name

(7S,9S)-7-[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione

Canonical SMILES

CC1C(C(CC(O1)OC2CC(CC3=C2C(=C4C(=C3O)C(=O)C5=C(C4=O)C(=CC=C5)OC)O)(C(=O)CO)O)N)O

InChI

InChI=1S/C27H29NO11/c1-10-22(31)13(28)6-17(38-10)39-15-8-27(36,16(30)9-29)7-12-19(15)26(35)21-20(24(12)33)23(32)11-4-3-5-14(37-2)18(11)25(21)34/h3-5,10,13,15,17,22,29,31,33,35-36H,6-9,28H2,1-2H3/t10-,13-,15-,17-,22+,27-/m0/s1

InChIKey

AOJJSUZBOXZQNB-TZSSRYMLSA-N

Density

1.615±0.10 g/cm3

Solubility

Soluble in DMF, DMSO, Ethanol, Methanol, Water (Poorly)

Melting Point

204-205 °C

Flash Point

443.8°C

Index Of Refraction

1.709

Optical Rotation

Specific optical rotation: +248 deg at 20 °C/D (0.1% in methanol)

PSA

206.07000

Vapor Pressure

9.64E-28mmHg at 25°C

UV Spectra

Max absorption (methanol at 56 °C): 290 nm (epsilon = 145, 1%, 1 cm); 477 nm (epsilon = 225, 1%, 1 cm); 495 nm (epsilon = 223, 1%, 1 cm); 530 nm (epsilon = 124, 1%, 1 cm); 233 nm (epsilon = 658, 1%, 1 cm); 253 nm (epsilon = 440, 1%, 1 cm)

Source

Streptomyces peucetius

Appearance

Orange to Red Powder

Shelf Life

Neutral aq soln are stable at room temp

Shipping

-20°C (International: -20°C)

Storage

Store at -20 °C

Pictograms

Irritant; Health Hazard

Signal Word

Danger

Boiling Point

810.3±65.0 °C at 760 mmHg

Current Developer

Janssen Pharmaceutical K.K.

In Vitro

Peritoneal macrophages from BD IX rats collected 24 hr after an i.p. injection of Adriamycin (10 mg/kg) were cytotoxic to syngeneic cancer cells in culture. In contrast, incubation in vitro in Adriamycin solutions did not evoke tumoricidal activity in peritoneal macrophages, whatever the incubation time (from 1 to 24 hr) and the Adriamycin concentration (from 1 ng to 100 micrograms/ml).

In Vivo

Macrophages incubated with Adriamycin in vitro accumulated the drug in their nuclei, whereas macrophages from animals receiving Adriamycin in vivo accumulated it is cytoplasmic vacuoles. Early observation of peritoneal cells after in vivo exposure to Adriamycin shows that Adriamycin is concentrated in mast cell granules which are released and then phagocytosed by peritoneal macrophages. Adriamycin fluorescence appears in nuclei of cancer cells incubated with in vivo-labeled macrophages, suggesting that macrophages can directly transfer the drug into cancer cells and therefore play a role in the Adriamycin antitumor effect.

Mechanism Of Action

Doxorubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action: Doxorubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes.

Pharmacology

Doxorubicin is an antineoplastic in the anthracycline class. General properties of drugs in this class include: interaction with DNA in a variety of different ways including intercalation (squeezing between the base pairs), DNA strand breakage and inhibition with the enzyme topoisomerase II. Most of these compounds have been isolated from natural sources and antibiotics. However, they lack the specificity of the antimicrobial antibiotics and thus produce significant toxicity. The anthracyclines are among the most important antitumor drugs available. Doxorubicin is widely used for the treatment of several solid tumors while daunorubicin and idarubicin are used exclusively for the treatment of leukemia. Doxorubicin may also inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA. Doxorubicin possesses an antitumor effect against a wide spectrum of tumors, either grafted or spontaneous. The anthracyclines are cell cycle-nonspecific.

Toxicity (LD50)

LD50=21800 ug/kg (rat, subcutaneous).

NCT Number	Condition Or Disease	Phase	Start Date	Sponsor	Status
NCT03023124	Solitary Fibrous Tumors	Phase 2	2021-11-01	Italian Sarcoma Group	Recruiting
NCT01404936	Lymphoma	Phase 2	2013-02-01	M.D. Anderson Cancer Center	Completed
NCT00107094	Breast Cancer	Phase 1	2007-07-20	Celgene Corporation	Completed
NCT03505164	Doxorubicin Adverse Reaction		2021-04-27	Rush University Medical Center	Completed
NCT03027063	Breast Cancer Female	Not Applicable	2021-01-05	Johns Hopkins University	Completed

1. Multiwalled carbon nanotube–doxorubicin supramolecular complexes for cancer therapeutics

Hanene Ali-Boucetta, Khuloud T. Al-Jamal, Kostas Kostarelos*. Chem. Commun., 2008, 459–461

In this communication, we describe a previously unreported non-covalent multiwalled nanotube (MWNT)–doxorubicin supra-molecular complex that can be developed for cancer therapy. We have investigated the ability of doxorubicin to interact non-covalently with very thin, pristine MWNT 1 at various mass ratios and evaluated their capability to kill human breast cancer cells. Doxorubicin belongs to a clinically-used family of anthracyclines, therefore constitutes one of the best candidates to test non-covalent complexation with MWNTs. Moreover, doxorubicin 3 is a fluorescent molecule with a chromophore composed of three planar and aromatic hydroxyanthraquinonic rings that are used to monitor its supramolecular interaction with MWNTs. MWNTs were dispersed in water using the tri-block copolymer.

2. Synthesis, in vitro and in vivo anticancer activity of novel 1-(4-imino-1-substituted-1H-pyrazolo[3,4-d] pyrimidin-5(4H)-yl)urea derivatives

Chandra Bhushan Mishra, Raj Kumar Mongre, Shikha Kumari, Dong Kee Jeong* and Manisha Tiwari*. RSC Adv.,2016, 6, 24491–24500

To study apoptosis by flow cytometer, A549 cells were treated with CBS-1 (5 μM and 10 μM) and doxorubicin (10 μM) for 24 h. In result, CBS-1 at 10 μM concentration showed significant (p <0.05) apoptosis against A549 cells and it was found better than doxorubicin (10 μM) as shown in Fig. 6 and Table 3. Result points out that CBS-1 (10 μM) showed 50.98% apoptosis and while doxorubicin (10 mM) displayed 22.74% apoptosis in 24 h. Thus, Hoechst 33342 staining and flow cytometry studies evidently indicate that CBS-1 (10 mM) showed better apoptosis against A549 cells as compared to doxorubicin.

3. Multifunctional ATRP based pH responsive polymeric nanoparticles for improved doxorubicin chemotherapy in breast cancer by proton sponge eﬀect/endo-lysosomal escape

Shantanu V. Lale, Arun Kumar, Farhat Naz, Alok C. Bharti and Veena Koul*. Polym. Chem.,2015, 6,2115–2132

Polymer nanoparticles (NPs) for doxorubicin delivery in breast cancer have been investigated by many researchers to overcome the cardiotoxicity, non-specificity and acquired resistance of cancer cells to current doxorubicin chemotherapy. Polymeric nanoparticles help to improve the bioavailability of doxorubicin by passive targeting of tumors via an enhanced permeation and retention (EPR) eﬀect, by increasing the circulation half-life of doxorubicin and by overcoming acquired cancer cell resistance. These polymeric nanosystems suﬀer from few drawbacks, which lead to a decreased antitumor eﬃcacy of doxorubicin. Doxorubicin hydrochloride is a water-soluble drug, which makes it diﬃcult to physically load doxorubicin into nanoparticles in suﬃcient amounts.

Catalog	Product Name	CAS
BADC-01360	Daunorubicin citrate	1884557-85-0
BADC-00042	Daunorubicin	20830-81-3
BADC-00041	Daunorubicin hydrochloride	23541-50-6
BADC-00685	MCC-Modified Daunorubicinol	721945-30-8