Genotoxicity of the Hydroquinone Metabolite of Ochratoxin A:  Structure-Activity Relationships for Covalent DNA Adduction

2006 ◽  
Vol 19 (9) ◽  
pp. 1241-1247 ◽  
Author(s):  
Mariana Tozlovanu ◽  
Virginie Faucet-Marquis ◽  
Annie Pfohl-Leszkowicz ◽  
Richard A. Manderville
Keyword(s):  
Ochratoxin A ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Dna Adduction

On the role of copper and iron in DNA cleavage by ochratoxin A. Structure-activity relationships in metal binding and copper-mediated DNA cleavage

1998 ◽  
Vol 76 (6) ◽  
pp. 907-918 ◽  
Author(s):  
Jason A Ardus ◽  
Ivan G Gillman ◽  
Richard A Manderville
Keyword(s):  
Ochratoxin A ◽  
Chlorine Atom ◽  
Metal Binding ◽  
Dna Cleavage ◽  
Aqueous Media ◽  
Reducing Agent ◽  
Sodium Ascorbate ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Dna Adduction

Ochratoxin A (OTA, 1: X = Cl) is a fungal carcinogen that facilitates single-strand DNA cleavage and DNA adduction when metabolically activated. To determine if redox-active transition metals induce OTA-mediated DNA damage, we have examined the toxin's ability to bind Cu(II) and Fe(III) in aqueous media and facilitate DNA cleavage in their presence using agarose gel electrophoresis and supercoiled plasmid DNA. Using fluorescence spectroscopy, 1 was found to bind Cu(II) readily at physiological pH, while acidic conditions (pH 2.6) were employed to study Fe(III) binding due to the formation of Fe-oxide precipitates at higher pH values. Structure-activity relationships employing synthetic derivatives of 1 implied that 1 binds both Cu(II) and Fe(III) by its phenolic oxygen, while the carboxylic acid of its phenylalanine moiety binds Cu(II), but does not appear to play a role in Fe(III) coordination at pH 2.6. In terms of metal-mediated DNA cleavage, no role for 1 could be detected in Fe-induced DNA strand scission. With Cu(II), DNA cleavage by the 1:1 copper-bound complex of 1 could only be initiated by addition of a suitable reducing agent (sodium ascorbate). However, 1 was found to facilitate DNA cleavage by the Cu(II) complex of 1,10-phenanthroline (Cu(OP)2); a prototypical Cu-mediated nuclease system that cleaves DNA upon activation by an external reducing agent. Structure-activity relationships employing analogs lacking the chlorine atom, ochratoxin B (2: X = H), and the lactone (12), indicated that the chlorine atom is essential for activity of the OTA in potentiating DNA cleavage by Cu(OP)2. The implications of our findings to the genotoxic properties of 1 are discussed.Key words: ochratoxin, DNA cleavage, copper, iron, 1,10-phenanthroline.

scholarly journals Structure–Activity Relationships Imply Different Mechanisms of Action for Ochratoxin A-Mediated Cytotoxicity and Genotoxicity

2011 ◽  
Vol 25 (1) ◽  
pp. 181-190 ◽  
Author(s):  
Kheira Hadjeba-Medjdoub ◽  
Mariana Tozlovanu ◽  
Annie Pfohl-Leszkowicz ◽  
Christine Frenette ◽  
Robert J. Paugh ◽  
...  
Keyword(s):  
Ochratoxin A ◽  
Mechanisms Of Action ◽  
Structure Activity Relationships ◽  
Structure Activity

Toxicity of Ochratoxin A, Its Opened Lactone Form and Several of Its Analogs: Structure–Activity Relationships

1996 ◽  
Vol 137 (2) ◽  
pp. 182-192 ◽  
Author(s):  
Hao Xiao ◽  
Srinivasa Madhyastha ◽  
Ronald R. Marquardt ◽  
Suzhen Li ◽  
Jayantha K. Vodela ◽  
...  
Keyword(s):  
Ochratoxin A ◽  
Lactone Form ◽  
Structure Activity Relationships ◽  
Structure Activity

Structure–activity relationships for the fluorescence of ochratoxin A: Insight for detection of ochratoxin A metabolites

2008 ◽  
Vol 617 (1-2) ◽  
pp. 153-161 ◽  
Author(s):  
Christine Frenette ◽  
Robert J. Paugh ◽  
Mariana Tozlovanu ◽  
Maud Juzio ◽  
Annie Pfohl-Leszkowicz ◽  
...  
Keyword(s):  
Ochratoxin A ◽  
Structure Activity Relationships ◽  
Structure Activity

Structure-activity relationships in the acronycine and benzo[b]acronycine series: Role of the pyran ring

Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
Q Do ◽  
H Doan Thi Mai ◽  
T Gaslonde ◽  
B Pfeiffer ◽  
S Léonce ◽  
...  
Keyword(s):  
Pyran Ring ◽  
Structure Activity Relationships ◽  
Structure Activity

Structure activity-relationships of P-Glycoprotein modulation using a small library of macrocyclic lathyrane diterpenes

Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
M Reis ◽  
RJ Ferreira ◽  
MMM Santos ◽  
DJVA dos Santos ◽  
J Molnár ◽  
...  
Keyword(s):  
Structure Activity Relationships ◽  
Structure Activity ◽  
P Glycoprotein
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