%0 Journal Article
%T Physicochemical Mechanisms of Synergistic Biological Action of Combinations of Aromatic Heterocyclic Compounds
%A Maxim P. Evstigneev
%J Organic Chemistry International
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/278143
%X The mechanisms of synergistic biological effects observed in the simultaneous use of aromatic heterocyclic compounds in combination are reviewed, and the specific biological role of heteroassociation of aromatic molecules is discussed. 1. Introduction Biologically active aromatic compounds (BACs) constitute an important group of pharmaceutical drugs, extensively utilized in various medicinal applications. Typical examples are the aromatic anthracycline antibiotics (daunomycin, doxorubicin, topotecan, mitoxantrone, etc.), which are effective against solid tumors and leukemia; quinolone antibiotics (norfloxacin, ofloxacin, etc.), exerting a wide spectrum of antibacterial activity; aromatic vitamins (riboflavin, nicotinamide, etc.), used as antioxidants in chemotherapy; methylxanthines which are present in high concentrations in food sources; and many other aromatic compounds, possessing useful medicobiological properties (Figure 1) [1, 2]. Figure 1: Structures of typical aromatic drug molecules: (a) daunomycin (R=H), (a) doxorubicin (R=OH), (b) topotecan, (c) mitoxantrone/novantrone, (d) actinomycin D, and (e) norfloxacin. Practically all of the aromatic antitumour drugs exert toxic side effects at high dose, which limits their use in clinical practice. In particular, the most effective antitumour anthracycline antibiotics are characterized by remarkable cardiotoxicity being developed within the first 2-3 days of the chemotherapy course with the possibility of lethal outcome at overdosing [3]. However, the risk of side toxicity may be significantly lowered, or the medicobiological effect amplified, by combination of these antibiotics with other drugs, for instance, with various antitumour aromatic antibiotics (known as a combinational chemotherapy) or vitamins [4¨C6]. Aromatic molecules are commonly represented in a form of planar heterocyclic structures, having a chromophore as a main part composed of conjugated C=C double bonds with delocalized -electrons. Numerous investigations of the behaviour of aromatic molecules in aqueous solutions have shown that vertical-stacking interactions for such compounds are the most important in solution resulting in the formation of ˇ°sandwichˇ±-type aggregates (Figure 2) with more than two monomers in the general case [6]. A distinction is usually made between self-association (interaction of identical molecules, Figure 2(a)) and hetero-association (interaction of different molecules, Figure 2(b)) [7, 8]. Figure 2: (a) Self-association and (b) hetero-association of planar aromatic molecules. Although the mechanisms of
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