| Abstract [eng] |
The increasing resistance of bacteria to antibiotics, the lack of new antiviral drugs and the worldwide annually growing number of cancer cases indicates that the synthesis of novel molecules with pharmacologically beneficial properties requires more attention. Widely examined various pyrrolidinone derivatives are characterized by a broad spectrum of biological properties. Some of the pyrrolidinone derivatives are the active ingredients of currently used drugs. Therefore, the aim of this project was to synthesize new potentially bioactive derivatives of 1-(2-hydroxy-5-methylphenyl)-5-oxopyrrolidine-3-carboxylic acid and to investigate their chemical and biological properties. After synthesis of 1-(2-hydroxy-5-methylphenyl)-5-oxopyrrolidine-3-carboxylic acid, its esterification was carried out, and the resulting ester was transformed into 1-(2-hydroxy-5-methylphenyl)-5-oxopyrrolidine-3-carbohydrazide during the hydrazinolysis reaction. The chemical properties of the obtained compound were investigated by performing condensation reactions with variously substituted aromatic, heterocyclic aldehydes and monoketones. Condensation reactions between the amino acid hydrazide and dicarbonyl compounds allowed to obtain different products – a reaction with 2,4-pentadione in the presence of a catalytic amount of hydrochloric acid resulted in derivative containing a pyrazole moiety, and a reaction with 2,5-hexanedione in the presence of a catalytic amount of acetic acid resulted in a derivative containing a pyrrole ring. Compounds containing the isatin moiety often exhibit diverse biological activity, thus isatin fragment containing derivative was obtained in condensation reaction of initial carbohydrazide with isatin. Hydrazide reacts with phenyliso(thio)cyanates and forms 2-[1-(2-hydroxy-5-methylphenyl]-5-oxopyrrolidine-3-carbonyl)-N-phenylhydrazine-1-carbo(thio)amides. After alkaline cyclization with 4 % NaOH, compounds containing a triazole ring were obtained. The initial carboxylic acid reacts with benzene-1,2-diamine derivatives, hence the Phillips condensation reactions were used to obtain new benzimidazole derivatives. Alkylation reactions are often used to increase the lipophilicity of molecules, therefore the alkylation of obtained hydrazones and benzimidazoles were investigated. As a result, mono- and dialkylated derivatives of these compounds were obtained. The antioxidant properties of the compounds were investigated by the DPPH spectrophotometric method. 1-(2-Hydroxy-5-methylphenyl)-4-(6-methyl-1H-benz[d]imidazol-2-yl)pyrrolidin-2-one demonstrated the strongest radical scavenging activity. Antibacterial activity against three gram-positive and two gram-negative bacterial strains were also tested. 1-(2-Hydroxy-5-methylphenyl)-N'-[(5-nitrothiophen-2-yl)methylene]-5-oxopyrrolidine-3-carbohydrazide and 1-(2-hydroxy-5-methylphenyl)-N'-[(5-nitrofuran-2-yl)methylene]-5-oxopyrrolidine-3-carbohydrazide held the strongest and broadest antibacterial effect. |
