Theoretical studies on interaction of anticancer drugs (dacarbazine,procarbazine and triethylenemelamine) with normal (AT and GC) and mismatch (GG,CC, AA and TT) base pairs

This study is an attempt to gain a better understanding of the physicochemical interaction between novel anticancer drugs and DNA bases. We have employed quantum chemical tools to explore the interaction of a few anticancer drugs namely procarbazine (PR), dacarbazine (DC) and triethylenemelamine (TR)] with isolated normal (GC and AT) and mismatch (AA, CC, GG and TT) base pairs. The molecular geometries, electronic structural stability, vibrational energies, chemical reactivity and other electronic properties were studied using MP2/6-311+G^**, B3LYP/6-311+G^** and M05-2X/6-311+G^** methods. The optimised geometries of the usual and mismatch base pairs are almost planar whereas the geometries of drug-interacting complexes deviate from planarity. The presence of steric hindrance and π-bond overlaps between C–C bonds in the complexes has distorted the planarity of the four- and five-member rings in the base pairs. Among the three drugs chosen, DC and PR bond well with normal and mismatch base pairs with large interaction energy. The electron density (ED) difference maps of the most stable GG–DC, GG–PR and GG–TR drug-interacting complexes show the information about sharing of ED and gain or loss of ED within the interacting molecules. The stabilisation energy of the charge transfer interaction between the relevant donor–acceptor orbital of GG–DC and GC–DC complexes has been found to be around 16 kcal/mol and GG–PR and GC–PR complexes has been found to be around 12 kcal/mol. But, for the GG–TR and GC–TR complexes, the stabilisation energy is found to be less than 6 kcal/mol. Moreover, the topological analysis of hydrogen bond network of DC and PR drug-interacting complexes have high electron and Laplacian density with structural stability at the bond critical points (BCPs), while compared TR drug-interacting complexes by atoms in molecules and natural bond orbital analysis. Finally, we may conclude that the drugs DC and PR are highly efficient drugs to target normal and mismatch base pair for control and inhibition of DNA replication.