3-AMINO-1,2,4-BENZOTRIAZINE-1,4-DIOXIDE Chemical Properties

Melting point:

220°C dec.

Boiling point:

493.6±28.0 °C(Predicted)

Density 

1.68±0.1 g/cm3(Predicted)

storage temp. 

-20°C

solubility 

DMSO: soluble10mg/mL, clear

form 

powder

pka

1.51±0.30(Predicted)

color 

orange to dark orange-red

InChI

InChI=1S/C7H6N4O2/c8-7-9-11(13)6-4-2-1-3-5(6)10(7)12/h1-4H,(H2,8,9)

InChIKey

ORYDPOVDJJZGHQ-UHFFFAOYSA-N

SMILES

[N+]1([O-])C2=CC=CC=C2[N+]([O-])=C(N)N=1

Safety Information

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26-36

WGK Germany 

3

RTECS 

DM0671500

HS Code 

2933.99.7500

3-AMINO-1,2,4-BENZOTRIAZINE-1,4-DIOXIDE Usage And Synthesis

Description

Tirapazamine is a hypoxia-activated anticancer agent. It is converted to an oxidizing radical under hypoxic conditions and can induce single- and double-strand breaks in DNA, formation of trapped topoisomerase I- and II-DNA complexes, and other chromosomal aberrations, leading to cytotoxicity. Tirapazamine induces hypoxia-enhanced cytotoxicity in DT40 cells (IC₅₀s = 1.02 and 4.34 μM in hypoxic and normoxic conditions, respectively). It also induces cytotoxicity in HT-1080 and A549 cells in a concentration-dependent manner under hypoxic conditions. In vivo, tirapazamine sensitizes tumors to cisplatin in a mouse RIF-1 fibrosarcoma tumor model. Tirapazamine (0.08 mmol/kg) also sensitizes tumors to fractionated irradiation in a FaDu hypopharyngeal squamous cell carcinoma mouse xenograft model.

Chemical Properties

Orange Needles

Uses

A bioreductive anticancer agent. Selectively toxic to cells under hypoxic conditions. An antineoplastic

Uses

Tirapazamine has been used to evaluate its cytotoxic effect on U-251 MG (glioblastoma cell line) cell viability.

Definition

ChEBI: A member of the class of benzotriazines that is 1,2,4-benzotriazine carrying an amino substituent at position 3 and two oxido substituents at positions 1 and 4.

Biochem/physiol Actions

Under hypoxic conditions, tirapazamine is a potent cytotoxic agent that induces apoptosis by inducing breaks in single and double stranded DNA, as well as chromosomal breaks. The compound sensitizes cells to other ionizing radiation and other cytotoxic agents like cisplatin.

References

[1] BROWN J. SR 4233 (Tirapazamine): a new anticancer drug exploiting hypoxia in solid tumours[J]. British Journal of Cancer, 1993, 67 6: 1163-1170. DOI: 10.1038/bjc.1993.220
[2] SRINI B REDDY  Stephen K W. Tirapazamine: a novel agent targeting hypoxic tumor cells.[J]. Expert opinion on investigational drugs, 2009, 18 1: 77-87. DOI: 10.1517/13543780802567250
[3] TAKAHITO MORIWAKI. Cytotoxicity of Tirapazamine (3-Amino-1,2,4-benzotriazine-1,4-dioxide)-Induced DNA Damage in Chicken DT40 Cells[J]. Chemical Research in Toxicology, 2016, 30 2: 699-704. DOI: 10.1021/acs.chemrestox.6b00417
[4] M J DORIE  J M B. Tumor-specific, schedule-dependent interaction between tirapazamine (SR 4233) and cisplatin.[J]. Cancer research, 1993, 53 19: 4633-4636.
[5] A EL SAID. Comparison of the effectiveness of tirapazamine and carbogen with nicotinamide in enhancing the response of a human tumor xenograft to fractionated irradiation.[J]. Radiation oncology investigations, 1999, 7 3: 163-169. DOI: 10.1002/(sici)1520-6823(1999)7:3<163::aid-roi5>3.0.co;2-m

3-AMINO-1,2,4-BENZOTRIAZINE-1,4-DIOXIDE(27314-97-2)Related Product Information

• Norfloxacin
• Gemcitabine
• POLYETHYLENEIMINE
• 3-Amino-7-chloro-1,2,4-benzotriazine 1,4-dioxide
• 1,2,4-benzotriazin-3-amine
• 3-AMINO-1,2,4-BENZOTRIAZINE-1,4-DIOXIDE
• 3-AMINO-1,2,4-BENZOTRIAZINE-1-N-OXIDE
• 3-AMINO-1,2,4-TRIAZINE