Nitracrine is a 1-nitroacridine derivative and is an effective hypoxia-selective agent in vitro and antitumor drugs. Nitracrine suppresses RNA synthesis and covalently, reversibly binds to DNA but also forms covalent adducts with DNA in vivo. Nitracrine h
Iproplatin is a synthetic second-generation platinum-containing compound related to cisplatin. Iproplatin binds to and forms DNA crosslinks and platinum-DNA adducts, resulting in DNA replication failure and cell death. Although less prone to glutathione i
MeIQx (MeIQx) is a food-derived carcinogen that has been found in high temperature-cooked fish and meats.1It is activated by hydroxylation and subsequent O-acetylationviathe cytochrome P450 (CYP) isoform CYP1A2 and N-acetyltransferase 2, respectively, in UV5 cells expressing the human enzymes to a metabolite that reacts with DNA to form adducts.2MeIQx (200 and 400 ppm in the diet) induces tumor formation in rats.3
DEPMPO is a nitrone that is used to spin trap reactive O-, N-, S-, and C-centered radicals and allow their characterization when used in association with electron spin resonance. It is noted for the stability of adducts formed. DEPMPO can be used in vitro or in vivo, as it crosses lipid bilayer membranes and is a good trapping agent in biological systems. DEPMPO-biotin is a biotinylated form of DEPMPO which retains the outstanding persistency of its adducts. The biotin moiety offers an effective means for monitoring biodistribution in cells, tissues, and organs when used with an avidin-conjugated reporter. Importantly, DEPMPO-biotin binds free radicals, such as S-nitroso groups, on proteins, producing adducts that can be analyzed via the biotin tag. This direct labeling of S-nitrosothiols (SNO) thus serves as an effective alternative to the more cumbersome biotin-switch method for monitoring SNO formation.
Monohydroxy melphalan is a DNA alkylating agent and a degradation product of melphalan . Monohydroxy melphalan is formed by the hydrolysis of melphalan in aqueous solutions, including cell culture medium and human plasma. It increases the level of DNA adducts in ML-1 myeloblastic leukemia cells in a concentration-dependent manner and induces cytotoxicity with an IC50 value of 28.1 μg ml.
N’-Nitrosonornicotine is a tobacco-specific N-nitrosamine and carcinogen that has been found in unburned tobacco and cigarette smoke.1It induces the formation of DNA adducts in isolated rat nasal mucosa and esophagus. N’-Nitrosonornicotine induces tumor formation in rat esophagus and nasal cavity, mouse lung, forestomach, and trachea, and hamster trachea and forebrain. Urinary levels of N’-nitrosonornicotine are positively correlated with the risk of esophageal cancer in smokers.2 1.Hecht, S.S.Biochemistry, biology, and carcinogenicity of tobacco-specific N-nitrosaminesChem. Res. Toxicol.11(6)559-603(1998) 2.Yuan, J.-M., Knezevich, A.D., Wang, R., et al.Urinary levels of the tobacco-specific carcinogen N’-nitrosonornicotine and its glucuronide are strongly associated with esophageal cancer risk in smokersCarcinogenesis32(9)1366-1371(2011)
cDPCP is a platinum-containing DNA-crosslinking agent.1Unlike cisplatin or oxaliplatin , cDPCP forms monofunctional DNA adducts. It is transported into cells by organic cation transporter 1 (OCT1) and OCT2, inhibiting proliferation of MDCK cells expressing the human transporters with IC50values of 8.1 and 1.5 μM, respectively. cDPCP inhibits RNA polymerase II-mediated transcription in a reporter assay using HeLa cells. It increases survival in murine S180 sarcoma and P388 leukemia models when administered at doses of 40 and 80 mg/kg, respectively.2 1.Lovejoy, K.S., Todd, R.C., Zhang, S., et al.cis-Diammine(pyridine)chloroplatinum(II), a monofunctional platinum(II) antitumor agent: Uptake, structure, function, and prospectsProc. Natl. Acad. Sci. USA105(26)8902-9807(2008) 2.Hollis, L.S., Amundsen, A.R., and Stern, E.W.Chemical and biological properties of a new series of cis-diammineplatinum(II) antitumor agents containing three nitrogen donors: cis-[Pt(NH3)2(N-donor)Cl]+J. Med. Chem.32128-136(1989)
Abacavir carboxylate is an inactive metabolite of the HIV-1 reverse transcriptase inhibitor abacavir . It is formed from abacavir via reactive aldehyde intermediates that can form adducts with proteins on valine residues.
IBTP is a lipophilic cation that is accumulated in mitochondria and forms stable thioether adducts in a thiol-specific manner. As a result, mitochondrial proteins that have changed thiol redox state following oxidative stress are selectively tagged with IBTP and can be separated by two-dimensional electrophoresis and isolated. IBTP-tagged proteins can also be evaluated by immunoblotting using an antibody directed against the triphenylphosphonium moiety of the IBTP molecule. IBTP has also been used as a mitochondria-targeted soft electrophile to inhibit mitochondrial oxidative phosphorylation.
Heliotrine N-oxide is the pyrrolizidine alkaloid (PA) N-oxide counterpart of Heliotrine. It induces the generation of pyrrolic DNA adducts, potentially initiating PA-induced liver tumors in vivo.