Model study on the sequence specific stacking by chromophore of an anticancer drug, acridine carboxamide with base pairs of DNA

1483-1494The study on the sequence specific binding of acridine-4-carboxamides with DNA has been an important topic in the design of new drugs. It has been known that the anticancer properties of acridine-2, acridine-3 and acridine-4-carboxamides are significantly different. So the sequence specific binding of these drugs can be monitored from the intercalative mode of binding by chromophores within DNA. The stacking energies obtained from ab initio, MP2 and DFT methods have been used to understand the sequence preference intercalation by chromophore. Among these drugs, the acridine-4-carboxamide shows maximum stacking with GC base pair in spite of acquiring high potency, but the stacking energy of this drug with AT base pair is not so small. The conformation of carboxamide side chain in acridine-4-carboxamide does not lie in the same plane of chromophore, and also the orientation of side chain in acridine-2 and acridine-3 carboxamides is different from that of acridine-4-carboxamide