NLA 1

Description

NLA 1 is N-[3-(2-nitroimidazol-1-yl)propyl]acridin-9-amine hydrochloride, a compound of the nitroimidazole class, combined in one molecule with an acridine core. The acridine fragment reversibly intercalates into DNA, the 2-nitroimidazole fragment is responsible for radiosensitization, and the amino group in the propyl bridge increases the affinity for DNA and hydrophilicity. Record PubChem CID 368824.

Basic Attributes

• CAS No: 140448-36-8
• Chemical formula: C19H18ClN5O2
• Molecular Weight: 383.83200
• Exact mass: 383.1149025 g/mol
• NSC number: 640116
• PSA Specifications: 88.56000
• XLogP3: 5.39310

Physical properties

• Boiling point: 648.2 °C at 760 mm Hg. Art.
• Flash point: 345.8 °C
• Steam pressure: 1.1 × 10⁻¹⁶ mm Hg. Art. at 25 °C

Purpose and mechanism of action

The compound was developed as a bioreductive radiosensitizer of hypoxic tumor cells. The action scheme is two-stage: the acridine cycle retains the molecule on DNA due to intercalation, which increases the local concentration of the sensitizer at the target and reduces the availability of the nitro group for cellular reductases. The nitro group of 2-nitroimidazole is reduced under conditions of oxygen deficiency, hence the selectivity for hypoxic tissue.

• binding to DNA is reversible, comparable in affinity to 9-aminoacridine
• as a cytotoxin approximately 1000 times more active than misonidazole with a similar reduction potential
• increase in cytotoxicity in hypoxia - 5–6 times (for misonidazole about 11 times)
• concentration for gain factor 1.6 (C1.6) in AA8 cells: 9 µM

Scope of application

Reagent for laboratory research: radiobiology, study of tumor hypoxia, screening of bioreductive agents, work on targeted delivery to DNA. The drug has not been introduced into clinical practice.

Storage and handling

Hydrochloride salt, store in a closed container away from moisture and light. Work with the connection in a fume hood, wearing gloves and safety glasses. Nitroimidazoles and aminoacridines are considered potentially mutagenic; contact with skin and inhalation of dust should be avoided.