54301-15-4

Basic information

• Product Name: Amsacrine hydrochloride
• Synonyms: Methanesulfonamide, N-4-(9-acridinylamino)-3-methoxyphenyl-, monohydrochloride;M-Amsacrine;META-AMSACRINE;m-AMSA, 4-(9-Acridinylamino)-N-(methanesulfonyl)-m-anisidine hydrochloride;Methanesulfone-m-anisidine-4'-[(9-acridinyl)amino] hydrochloride;Methanesulfon-m-anisidide 4'-(9-acridinylamino)-;Methansulfon-m-aniside, 4'-(9-acridinylamino)-, monohydrochloride;N-(4-(acridin-9-ylaMino)-3-Methoxyphenyl)MethanesulfonaMide hydrochloride
• CAS NO: 54301-15-4
• Molecular Formula: C₂₁H₁₉N₃O₃S*ClH
• Molecular Weight: 429.92
• EINECS: 257-094-3
• Mol File: 54301-15-4.mol

Chemical Properties

• Melting Point: 197-199 °C(lit.)
• Boiling Point: 563°C at 760 mmHg
• Flash Point: 294.3°C
• Appearance: red to brown/powder
• Vapor Pressure: 1.06E-12mmHg at 25°C
• Storage Temp.: Refrigerator
• Solubility: DMSO: 10 mg/mL with heat and sonication
• CAS DataBase Reference: Amsacrine hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: Amsacrine hydrochloride(54301-15-4)
• EPA Substance Registry System: Amsacrine hydrochloride(54301-15-4)

Safety Data

• Hazard Codes: T
• Statements: 25-36/37/38
• Safety Statements: 26-45
• RIDADR: UN 2811 6.1/PG 3
• WGK Germany: 3
• RTECS: PB1081000
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 54301-15-4(Hazardous Substances Data)

Usage

Uses

Used in Anticancer Applications:
Amsacrine hydrochloride is used as a topoisomerase poison for various applications in the field of cancer research and treatment. It has been utilized in several assays and cell lines, such as:
As a topoisomerase poison in bacteriophage T4 topoisomerase assay, where it helps study the interaction between the drug and the enzyme responsible for DNA untangling during replication.
As a topoisomerase inhibitor in the Drosophila cell line, Kc167, which aids in understanding the drug's effect on cancer cell growth and its potential as a therapeutic agent.
As an antileukemia drug to test its effect on p53 transcriptional activity in tumor xenografts, which is essential for understanding the drug's role in regulating cancer-related genes and its overall impact on cancer progression.
As a topoisomerase II poison in dose-response assays in C. elegans, a model organism used to study the drug's efficacy and potential side effects in a living system.

Biological Activity

amsacrine hydrochloride (amsidine, m-amsa) is an inhibitor of topoisomerase 2 [1].amsacrine hydrochloride is a chemotherapy drug of antineoplastic, used to treat some types of lymphoma and acute leukaemia. in addition, amsacrine hydrochloride has shown the sensitivities to the cancer cell lines with the ic50 values of 190.2±27.4ng/ml, 46.1±3.9ng/ml,22.6±3.1ng/ml, 11.8±2.0ng/ml, 5.0±0.4ng/ml, and 11.7±1.5ng/ml for three bladder cancer cell lines (ht1376,rt112, rt4) and three testis cancer cell lines(833k, susa, gh), respectively. and it has been found that the testis tumor cell lines are more sensitive to inhibiting by amsacrine hydrochloride than the bladder cell lines [1].

Biochem/physiol Actions

Amsacrine (m-AMSA) is a derivative of acridine and an antileukemia drug. It is an anticancer drug with antineoplastic activity that targets topoisomerase II. AMSA is an apoptosis inducer and favors the accumulation of double-stranded breaks (DSBs). It also inhibits the expression of matrix metallopeptidase 2 (MMP-2) and MMP-9 expression in leukemia cells by generating reactive oxygen species (ROS). AMSA serves as an adjuvant in trabeculectomy surgery.

references

[1] nelson em, tewey km, liu lf. mechanism of antitumor drug action: poisoning of mammalian dna topoisomerase ii on dna by 4'-(9-acridinylamino)-methanesulfon-m-anisidide. proc natl acad sci u s a. 1984 mar;81(5):1361-5.

InChI:InChI=1/C21H19N3O3S.ClH/c1-27-20-13-14(24-28(2,25)26)11-12-19(20)23-21-15-7-3-5-9-17(15)22-18-10-6-4-8-16(18)21;/h3-13,24H,1-2H3,(H,22,23);1H

Upstream product

• 1207-69-8 9-Chloroacridine 
• 57165-06-7 N-(4-amino-3-methoxyphenyl)methanesulfonamide 
• 57165-05-6 3-methoxy-4-nitro-N-(methylsulfonyl)benzenamine 
• 16292-88-9 3-methoxy-4-nitroanilin 
• 20628-19-7 N-(3-methoxy-4-nitrophenyl)acetamide 

Relevant articles and documents

Potential Antitumor Agents. 48. 3'-Dimethylamino Derivatives of Amsacrine: Redox Chemistry and in Vivo Tumor Activity

Structure-activity relationships for a series of acridine-substituted 3'-N(CH3)2 derivatives of the clinical antileukemic drug amsacrine (1) are reported.The parent (unsubstituted) compound 3 has activity against the Lewis lung solid tumor that is superior to amsacrine(1), the new clinical amsacrine analogue 4, and the recently developed 3'-NHCH3 derivative 2.Although the compounds generally bind less well to DNA and are less dose potent in vivo than either their amsacrine (3'-OCH3) or 3'-NHCH3 analogues, they show very high levels of antitumor activity, with the 4-OCH3 derivative capable of effecting 100percent cures of the Lewis lung solid tumor.The broad structure-activity relationships for acridine substitution more closely resemble those of the amsacrine than the 3'-NHCH3 series, with 4-substituted and 4,5-disubstituted compounds showing the highest activity.

Multi-step process for the production of methanesulfon-m-anisidide, 4'-(9-acridinylamino)-

A multi-step method of producing the compound methanesulfon-m-anisidide, 4''-(9-acridinylamino)-, acetate (VII), which may be in free base form and designated NSC 249992, also known as AMSA. This compound is produced by an elegant process from a starting material, 4-butyrylamino-3-methoxy-nitrobenzene, which is later transformed to methanesulfon-m-anisidide, 4''-amino- (IV) and is coupled or joined to 9-chloro-acridine, producing the chloride salt which is later converted to the acetate.