Comparative Molecular Modeling Study of Binding of Mitoxantrone with D-(atcgat)2 and D- (ctcgag)2 Hexamer Dna Sequences

Mitoxantrone (MTX) 1, 4–dihydroxy–5, 8–bis [[2–[2–hydroxyethyl) amino] amino]–9, 10– anthracenedione is, clinically well established anthracycline class of anticancer drug. Till today no structural details confirm the interaction of mitoxantrone with its receptor site i.e. DNA Although it has been proposed and confirmed that drug binds to DNA specifically at 5’-CpG-3’ site and flanking sequences play an important role. Also, functional group present on the tricyclic aromatic chromophore plays vital role in interactions. Molecular modeling tool has been applied to study binding interaction of mitoxantrone (MTX) with two hexameric DNA sequences i.e d-(ATCGAT)2, d-(CTCGAG)2 . The electrostatic interactions play a vital role in sequence specific identification at receptor site. Study indicates the partial intercalation of mitoxantrone into 5’-CpG-3’ base pair step while side chains at 5, 8 position interacts with backbone phosphate group futher stabilizes the complex. The conformation flexibility of the minimized complex is studied by backbone torsional angle as well helical parameters. It has been seen that MTX exhibit sequence specific binding. It is n+1, n+2, n+3/n-1, n-2/n-3 base pairs play important role in binding process. Studies propose the partial intercalation mode of binding.