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. 2012 Mar 26;18(13):3850-4.
doi: 10.1002/chem.201200075. Epub 2012 Feb 29.

ROS-inducible DNA cross-linking agent as a new anticancer prodrug building block

Sheng Cao  1 , Yibin Wang, Xiaohua Peng
Affiliations

ROS-inducible DNA cross-linking agent as a new anticancer prodrug building block

Sheng Cao et al. Chemistry. .
No abstract available

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Figures

Figure 1
Figure 1
Concentration dependence of compounds 1-3 for DNA cross-link formation upon H2O2 activation. Lane 1: DNA only (cross-linking yield 0%); lane 2: DNA with 1 (2 mM) only (cross-linking yield 0%); lane 3: DNA with 2 (2 mM) only (cross-linking yield 0%); lane 4: DNA with 3 (2 mM) only (cross-linking yield 0%); lane 5: DNA with H2O2 (10 μM) only (cross-linking yield 0%); lane 6: 10 μM 1 + 5 μM H2O2 (0%); lane 7: 100 μM 1 + 50 μM H2O2 (0%); lane 8: 2 mM 1 + 1 mM H2O2 (0%); lane 9: 10 μM 2 + 5 μM H2O2 (2%); lane 10: 100 μM 2 + 50 μM H2O2 (8%); lane 11: 2 mM 2 + 1 mM H2O2 (24%); lane 12: 10 μM 3 + 5 μM H2O2 (0%); lanes 13: 100 μM 3 + 50 μM H2O2 (0%); lane 14: 2 mM 3 + 1 mM H2O2 (0%).
Figure 2
Figure 2
Selectivity of 2 (400 μM) with various reactive oxygen species (ROS) at 200 μM. Data were acquired at 25 °C in 10 mM phosphate buffer, pH 8, after 48 h.
Figure 3
Figure 3
1H NMR kinetic analysis of 2 in mixture of deuterated DMSO (550 μL) and D2O (96 μL) with 57.7 mM H2O2 and 23.1 mM 2; (B) 30 min after addition of H2O2; (C) 3 h after addition of H2O2; (D) 24 h after addition of H2O2. In addition, (A) sample 2 in deuterated DMSO only as a reference.
Scheme 1
Scheme 1
Synthesis of compound 2.
Scheme 2
Scheme 2
The structure of compounds 6, 8, and 10 generated from the reaction of 2, 1, and 3 with H2O2.
Scheme 3
Scheme 3
Tandem QM generation and ICL formation induced by 2 upon H2O2-activation.
Scheme 4
Scheme 4
Trapping reactions in the presence of EVE.
See this image and copyright information in PMC

References

    1. Noll DM, Mason TM, Miller PS. Chem. Rev. 2006;106:277–301. - PMC - PubMed
    2. Dronkert MLG, Kanaar R. Mutat. Res. 2001;486:217–247. - PubMed
    1. Rink SM, Solomon MS, Taylor MJ, Rajur SB, McLaughlin LW, Hopkins PB. J. Am. Chem. Soc. 1993;115:2551–2557.
    2. Tomasz M. Chemistry & Biology. 1995;2:575–579. - PubMed
    3. Sherman SE, Lippard SJ. Chem. Rev. 1987;87:1153–1181.
    4. Cimino GD, Gamper HB, Isaacs ST, Hearst TE. Annu. Rev. Biochem. 1985;54:1151–1193. - PubMed
    1. Hong IS, Greenberg MM. J. Am Chem. Soc. 2005;127:10510–10511. - PMC - PubMed
    2. Hong IS, Ding H, Greenberg MM. J. Am. Chem. Soc. 2006;128:485–491. - PMC - PubMed
    3. Peng X, Hong IS, Li H, Seidman MM, Greenberg MM. J. Am. Chem. Soc. 2008;130:10299–10306. - PMC - PubMed
    1. Zeng Q, Rokita SE. J. Org. Chem. 1996;61:9080–9081.
    2. Veldhuyzen WF, Pande P, Rokita SE. J. Am. Chem. Soc. 2003;125:14005–14013. - PubMed
    3. Wang H, Rokita SE. Angew. Chem. 2010;122:6093–6096.
    4. Angew. Chem. Int. Ed. 2010;49:5957–5960. - PubMed
    5. Weinert EE, Dondi R, Colloredo-Melz S, Frankenfield KN, Mitchell CH, Freccero M, Rokita SE. J. Am. Chem. Soc. 2006;128:11940–11947. - PMC - PubMed
    6. Wang H, Wahi MS, Rokita SE. Angew. Chem. 2008;120:1311–1313. - PubMed
    7. Angew. Chem., Int. Ed. 2008;47:1291–1293. - PubMed
    1. Richter SN, Maggi S, Mels SC, Palumbo M, Freccero M. J. Am. Chem. Soc. 2004;126:13973–13979. - PubMed
    2. Antonio MD, Doria F, Richter SN, Bertipaglia C, Mella M, Sissi C, Palumbo M, Freccero M. J. Am. Chem. Soc. 2009;131:13132–13141. - PubMed
    3. Verga D, Nadai M, Doria F, Perciballe C, Antonio MD, Palumbo M, Richter SN, Freccero M. J. Am. Chem. Soc. 2010;132:14625–14637. - PubMed
    4. Modica E, Zanaletti R, Freccero M, Mella M. J. Org. Chem. 2001;66:41–52. - PubMed

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