Cinnoline Analogs of Quinolones: Structural Consequences of the N Atom Introduction in the Position 2
According to a mechanism of inhibition of DNA-gyrase complex by quinolones proposed by Shen [I], the drug binds guanine base of a single stranded bacterial DNA. One of the consequences of this model is that binding energy depends on negative partial charges on O(4) and O(3) atoms (Fig.1), i.e. the greater negative charges the stronger will be the hydrogen bonds with guanine. We assume that introduction of N atom(s) into aromatic rings system of quinolones should affect partial charges on the O(4) and O(3). As positions 3,4 and 7 in quinolones are usually substituted, the remaining positions for N substitution are 2,5,6 and 8 (Fig.1). Some of them exert significant effects on structural and electronic properties of the quinolone analogs.