DNA-Binding Properties of Nonsymmetric Fluorenone Derivatives

Understanding the mechanisms of biological action of xenobiotics is a necessary condition for the targeted synthesis of promising drugs. This knowledge is especially important for the development of antiviral preparations, since the obligate parasitism of viruses leads to difficulties in differentiating pathological and normal processes in the living cell [1]. One of the most promising groups of antiviral drugs are interferon inductors. Among low-molecular-weight representatives of this group, the leading position belongs to amyxin (I), a low-toxicity polymodal agent used in clinical practice as an antiviral drug and immunomodulant. The antiviral and interferon-inducing action of this agent are related to its ability to intercalate into DNA [2]. The intercalation properties of amyxin probably also explain many other effects of this drug: inhibition of the transcription of nucleic acids [3], including reverse transcription [4, 5], suppression of the reproduction of phages in microbial cells [6], selective inhibition of the synthesis of viral proteins in infected cells [7], etc. The DNA-intercalating ability of amyxin was studied by various methods [8 – 10]. It was established that, in addition to stacking interactions, the considerable contribution to stabilization of the intercalation complex is due to the electrostatic interaction of protonated side amino groups with phosphates [11]. However, which one of the two interactions is more important is still under discussion [12]. In the series of amyxin analogs, the intercalation behavior has been studied only for symmetric dibasic fluorenones, while the properties of nonsymmetric derivatives remained uninvestigated. In this context, we have studied the intercalation properties of amyxin (I) and its monobasic and nonsymmetric dibasic analogs (II – VI) R = –O(CH2)2N(C2H5)2; R = H (I); R = –OC2H5; R = H (II); R = –OH; R = H (III); R = H; R = H (IV);