Galina Alexandrovna Zheltukhina

Amino acid and peptide hemin derivatives as new promising virucidal agents

We synthesized a series of hemin derivatives (HDs) substituted by residues of amino acids and peptides at either one or two propionic-acid residues, and studied the virucidal activity of the compounds obtained against herpes simplex virus. Compounds 6,7-bis-(methyl ester N0 L-seryl)-protohemin (IX) (2) and 6,7-bis-[methyl ester N0-L-arginyl)-protohemin (IX) (6) shown the highest virucidal activity. We also investigated the interaction between HDs and lipid-membrane components as a possible mechanism of virucidal action. A model system including Clarks electrode and a micellar solution of methyl linoleate was used to quantitatively assess the capability of HDs to catalyze the oxidation of polyunsaturated fatty acids as components of lipid membranes. Another model system including liposomes that consisted of dioleoylphosphatydylcholine and was loaded with the fluorescent dye carboxyfluorescein was employed to examine the effect of HDs on lipid-membrane permeability. The kinetics and efficacy of increasing liposome-membrane permeability on exposure to HDs appeared to depend on the nature of the substituents in the HDs. The findings are strongly suggestive of the presence of two different modes of interaction between an HD and the lipid membrane, i.e. oxidative and non-oxidative mechanisms possibly underlie the virucidal action of HDs.

Synthesis, Anti-MRSA, and Anti-VRE Activity of Hemin Conjugates with Amino Acids and Branched Peptides

The increasing prevalence of antibiotic‐resistant bacterial strains has necessitated the synthesis of novel antibacterial agents. It was previously shown that naturally occurring metalloporphyrin hemin possesses dark antibacterial activity against Gram‐positive bacteria. To improve hemin antibacterial activity, we synthesized a number of hemin conjugates with amino acids and branched peptides. Arginine‐containing hemin conjugates demonstrated high antibacterial activity against Gram‐positive bacteria including methicillin‐ and vancomycin‐resistant strains in vitro. Most of the synthesized conjugates showed low toxicity against human erythrocytes and leukocytes.