127191-86-0

Basic information

• Product Name: 7-(deoxyadenosin-N(6)-yl)aristolactam I
• Synonyms: 7-(deoxyadenosin-N(6)-yl)aristolactam I;7-(2'-Deoxyadenosin-N6-yl)aristolactam I
• CAS NO: 127191-86-0
• Molecular Formula: C27H22N6O7
• Molecular Weight: 542.49958
• Mol File: 127191-86-0.mol
• Article Data: 1

Chemical Properties

• Boiling Point: °Cat760mmHg
• Flash Point: °C
• Appearance: /
• Density: 1.87±0.1 g/cm3 (20 ºC 760 Torr)
• Refractive Index: 1.89
• CAS DataBase Reference: 7-(deoxyadenosin-N(6)-yl)aristolactam I(CAS DataBase Reference)
• NIST Chemistry Reference: 7-(deoxyadenosin-N(6)-yl)aristolactam I(127191-86-0)
• EPA Substance Registry System: 7-(deoxyadenosin-N(6)-yl)aristolactam I(127191-86-0)

Safety Data

• Hazardous Substances Data: 127191-86-0(Hazardous Substances Data)

Usage

General Description

7-(deoxyadenosin-N(6)-yl)aristolactam I, also known as dA-AL-I, is a potent and genotoxic compound that is formed from the reaction between aristolochic acid and DNA. It has been found to be a major contributing factor in the development of aristolochic acid-induced nephropathy and upper urinary tract carcinomas. dA-AL-I forms covalent adducts with DNA, leading to mutations and ultimately causing cancer. Due to its significant role in carcinogenesis, dA-AL-I has been the subject of extensive research in the field of toxicology and has led to increased awareness of the dangers associated with exposure to aristolochic acid-containing plants and herbal remedies.

InChI:InChI=1/C27H22N6O7/c1-37-14-4-2-3-11-18(14)21(22-19-12(27(36)32-22)5-15-24(20(11)19)39-10-38-15)31-25-23-26(29-8-28-25)33(9-30-23)17-6-13(35)16(7-34)40-17/h2-5,8-9,13,16-17,34-35H,6-7,10H2,1H3,(H,32,36)(H,28,29,31)

Upstream product

• 313-67-7 aristolochic acid I 
• 958-09-8 2'-deoxy-D-adenosine 

Relevant articles and documents

Comparison of Aristolochic acid I derived DNA adduct levels in human renal toxicity models

Aristolochic acid (AA) dependent human nephropathy results either from environmental exposure to Aristolochiaceae plant subspecies or their use in traditional phytotherapy. The toxic components are structurally related nitrophenanthrene carboxylic acids, i.e. Aristolochic acid I (AAI) and II (AAII). AAI is considered to be the major cause of Aristolochic acid nephropathy, characterized by severe renal fibrosis and upper urothelial cancer. Following enzymatic activation in kidney and/or liver, AAI metabolites react with genomic DNA to form persistent DNA adducts with purines. To determine whether AAI can be activated in human renal cells to form DNA adducts, we exposed telomerase immortalized renal proximal tubular epithelial cells (RPTEC/TERT1), the human embryonic kidney (HEK293) cell line, as well as primary human kidney cells (pHKC) to AAI in vitro. We modified an isotope dilution ultra-performance liquid chromatography/tandem mass spectrometry (ID-UPLC-MS/MS) based method for the quantification of dA-AAI adducts in genomic DNA. In addition, time dependent accumulation of adducts in renal cortex and bladder tissue from AAI/II treated Eker rats were used to validate the detection method. AAI-induced toxicity in human renal cells was determined by dA-AAI adduct quantification, the impact on cell viability, and NQO1 expression and activity. Our findings demonstrated adduct formation in all cell lines, although only pHKC and RPTEC/TERT1 expressed NQO1. The highest adduct formation was detected in pHKC despite low NQO1 expression, while we observed much lower adduct levels in NQO1-negative HEK293 cells. Adduct formation and decreased cell viability correlated only weakly. Therefore, our data suggested that i.) enzymes other than NQO1 could be at least equally important for AA bioactivation in human renal proximal tubule cells, and ii.) the suggested correlation between adduct levels and viability appears to be questionable.