Molecular modeling study of intercalation complexes of tricyclic carboxamides with d(CCGGCGCCGG) and d(CGCGAATTCGCG)

Athanasia Varvaresou (1) , Kriton Iakovou (2)

1 Laboratory of Cosmetology, Department of Aesthetics and Cosmetology
2 Ministry of Health and Social Solidarity

Tricyclic dyes with different mesoatoms such as xanthenes (fluorescein, eosin) anthracenes and acridines (proflavine) approved by the Food and Drug Administration (FDA) for use in foods, pharmaceuticals and cosmetic preparations interact with DNA, and some of them do so through intercalation. Hyperchem 7.5, Spartan 04, Yasara 10.5.14 program packages and molecular modeling, molecular mechanics and dynamics techniques with the oligonucleotides d(CCGGCGCCGG)2 and d(CGCGAATTCGCG)2 were utilized in order to examine the mode of binding to DNA of a range of tricyclic carboxamides bearing N,N-dimethylaminoethyl side chain, i.e., 9-amino-DACA, anthracene, acridine-1-carboxamide, acridine-4-carboxamide (DACA), azacridine, phenazine, pyridoquinoxaline, oxopyridoquinoxaline, phenoxazine and xanthenone or N,N-dimethylaminobutyl moiety, i.e., phenazine and acridine. The bicyclic quinoline-8-carboxamide was also examined for comparison reasons. On the basis of our data, prerequisite for the interaction between protonated N,N-dimethylaminoethyl moiety and guanine is the formation of only one internal hydrogen bond between carboxamide and NH + in the case of 9-amino-DACA or N in the cases of DACA, azacridine, phenazine and pyridoquinoxaline. The presence of an additional internal hydrogen bond between oxygen carboxamide and protonated N,N-dimethylamino group in the cases of tricyclic systems bearing NH (phenoxazine) or O (xanthenone) group, prevents the interaction between side chain and guanine. Also, the formation of one internal hydrogen bond between oxygen carboxamide and protonated N,N-dimethylamino group inhibits the interaction between side chain and guanine in the case of acridine-1-carboxamide. Our findings are in accordance with previously reported results obtained from the kinetic studies of the binding of acridine and related tricyclic carboxamides to DNA.

Mots clés: DNA intercalation; Molecular dynamic simulations; Molecular mechanics; Tricyclic dyes

Athanasia Varvaresou, Kriton Iakovou. Molecular modeling study of intercalation complexes of tricyclic carboxamides with d(CCGGCGCCGG) and d(CGCGAATTCGCG). Journal of Molecular Modeling, 2010, 17 (8), pp.2041-2050. ⟨10.1007/s00894-010-0891-5⟩. ⟨hal-00651659⟩