PMID- 11741482
OWN - NLM
STAT- MEDLINE
DCOM- 20020114
LR  - 20190710
IS  - 0022-2623 (Print)
IS  - 0022-2623 (Linking)
VI  - 44
IP  - 26
DP  - 2001 Dec 20
TI  - Structural basis for the binding affinity of xanthines with the DNA intercalator 
      acridine orange.
PG  - 4650-60
AB  - Caffeine (CAF), a methyl-substituted xanthine, interacts with polyaromatic DNA 
      intercalators and has been hypothesized to interfere with their intercalation 
      into DNA. Optical absorption spectroscopy was used to determine the binding 
      affinities (K(assoc)) and structural effects of a series of methyl-substituted 
      xanthines and a series of methyl-substituted uric acids (8-oxoxanthine) with the 
      known DNA intercalator acridine orange (AO). There is evidence that complexation 
      occurred (K(assoc) > or = 150 M(-1); binding curve saturation approximately > or 
      =50%) between AO and 1,7-dimethylxanthine (155 M(-1)), 1,3-dimethylxanthine 
      (theophylline, 157 M(-1)), 1,3,7-trimethylxanthine (CAF, 256 M(-1)), 
      1,3-dimethyl-8-chloroxanthine (413 M(-1)), 1,3,7,9-tetramethyl-8-oxyxanthine 
      (tetramethyl uric acid or TMU, 552 M(-1)), and theophylline ethylenediamine 
      (aminophylline, 596 M(-1)). No definitive evidence of complexation occurred 
      between AO and 16 other substituted xanthines or purines, although there was some 
      evidence of weak complexation (K(assoc) < 150 M(-1)) between AO and eight of the 
      sixteen. Three common structural similarities were identified among those 
      compounds found to form significant bonding with AO: (i) the N(1) or N(3) on the 
      xanthine structure must be substituted with a methyl group; (ii) oxygen or 
      chlorine substitution at C(8) increases binding affinity to AO when resonate 
      states remain unchanged; and (iii) K(assoc) increases with an increase in number 
      of methyl group substitutions on the 1- or 3-methylxanthine core structure. These 
      results are explained on the basis of complex stabilization due predominately to 
      hydrophobic attraction, with a contribution from charge transfer between donor 
      and acceptor components. This information can be used in the manipulation of the 
      physical or chemical characteristics of biologically active polyaromatic 
      molecules.
FAU - Lyles, M B
AU  - Lyles MB
AD  - Department of Cellular and Structural Biology, University of Texas Health Science 
      Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229, USA.
FAU - Cameron, I L
AU  - Cameron IL
FAU - Rawls, H R
AU  - Rawls HR
LA  - eng
GR  - DE00152/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Med Chem
JT  - Journal of medicinal chemistry
JID - 9716531
RN  - 0 (Intercalating Agents)
RN  - 0 (Xanthines)
RN  - F30N4O6XVV (Acridine Orange)
SB  - IM
MH  - Acridine Orange/*chemistry
MH  - Intercalating Agents/*chemistry
MH  - Methylation
MH  - Nonlinear Dynamics
MH  - Spectrophotometry
MH  - Structure-Activity Relationship
MH  - Xanthines/*chemistry
EDAT- 2001/12/14 10:00
MHDA- 2002/01/15 10:01
CRDT- 2001/12/14 10:00
PHST- 2001/12/14 10:00 [pubmed]
PHST- 2002/01/15 10:01 [medline]
PHST- 2001/12/14 10:00 [entrez]
AID - jm9904708 [pii]
AID - 10.1021/jm9904708 [doi]
PST - ppublish
SO  - J Med Chem. 2001 Dec 20;44(26):4650-60. doi: 10.1021/jm9904708.