**3.3. Antimicrobial drugs**

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 responses [59].

## **3.4. Simvastatin (hypocholesterolemic drug)**

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 potent and safer than SMS.

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