**Author details**

596 The Complex World of Polysaccharides

**3.3. Antimicrobial drugs** 

responses [59].

potent and safer than SMS.

**4. Conclusion** 

**3.4. Simvastatin (hypocholesterolemic drug)** 

2.3 lower than with 2-5 times larger SMS doses [60, 61].

their solubility in water. The GA complex with fluorouracil exerts antineoplastic action with respect to Pliss lymphosarcoma, B-16 melanoma, and Geren carcinoma. The effective indices are, respectively, 3.05; 2.11, and 1.76. The tumor growth inhibition is 67.2%; 53.4 %; 87.1 %.

GA complexes with antibiotiсs (chloramphenicol) and sulfanilamides (sulfamethoxypyridazine, saladimetoxine, sulfamonomethoxine, sulfadimidine, and sulfaguanidine), as well as with isoniazid and nitrofural, 1:1, were likewise synthesized in solution and compared in terms of their microbial activity. The highest survival rate (90%) was observed on the 10th day after exposure to infection in animals with staphylococcosis that received 50 mg/kg GA-chloramphenicol, while only 30% survived when pure chloramphenicol was given. The percentage of survived animals with *Pseudomonas aeruginosa*, *Proteus vulgaris*, and *E. coli* infections reached 80% on GA: chloramphenicol administration but it was only 20-50% on treatment with free chloramphenicol. The complex was also shown to stimulate humoral and cell immune

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (3HMG-CoA) reductase, the so-called statins, are known to successfully reduce low-density lipoproteins, and are used for this in atherosclerosis therapy. However, most statins cause side effects and have to be replaced by safer drugs, with a more prolonged action. NMR spectroscopy of the behavior of simvastatin (SMS) in solutions with GA indicates formation of stable complexes. The synthesized SMS:GA complex is stable in water solutions at GA above 0.2 mM [60]. The complex patented as simvaglysine (SMG) [61] demonstrates uncompetitive inhibition of 3HMG-CoA reductase. SMG, in doses with three times lower statin, turns out to be more

Thus, simvaglysine acts as an uncompetitive inhibitor/proinhibitor of the 3HMG-CoA reductase reaction by inducing inhibition of cholesterol synthesis in liver microsomal fraction of rats *in vitro*, being no less potent than simvastatin. Within the inhibition constants from 100 to 300 nM, SMS inhibits 37.7- 42.0% mevalonate formation, while SMG provides a 31-33% total blood cholesterol decrease after 14 days of administration in rats with hypercholesterolemia, at doses with 3 times lower SMS, which is as effective as the therapeutic dose of simvastatin. The greater safety of SMG is confirmed by a lower blood CPK (creatine phosphokinase) increase after 14 days of treatment than in the case of SMS:

Thus, water-soluble molecular complexes of various polysaccharides and glycyrrhizic acid with drugs that normally dissolve poorly in water have been synthesized and tested A. V. Dushkin *Institute of Solid State Chemistry and Mechanochemistry, Siberian Branch, Russian Academy of Sciences, Russia* 

T. G. Tolstikova, M. V. Khvostov and G. A. Tolstikov *N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Russia* 
