Synthesis and antimicrobial activity of fluorobenzoic acid amides

Abstract

The chemistry of organofluorine compounds, before the eyes of one generation, has turned from a small branch of organic chemistry into a large independent branch of exceptionally important theoretical and practical significance. Numerous studies have confirmed the high biological activity of a number of fluorine-containing organic compounds, as a result of which such drugs as fluoroquinolone antibiotics, risperidone, fluorophenazine, haloperidol, etc. have been created and are successfully used. Among amide derivatives, substances with antibacterial, anticonvulsant, analgesic and antifungal properties have been found. The purpose of this work is to develop ways to obtain a number of new potentially biologically active fluorine-containing amides based on morpholine, and to study their biological activity. Results and discussion: on the basis of cyclic amine - morpholine, by acylation with para-, meta-, ortho-fluorobenzoyl chlorides, reaction according to Schotten-Bauman, the corresponding amides of para-, meta-, ortho-fluorobenzoic acids were synthesized. The reaction was carried out in absolute benzene with cooling and the ratio of amine: acylating agent = 2:1. Inclusion complexes of compounds with b-cyclodextrin have been obtained. The composition and structure of the synthesized compounds were confirmed by data of elemental analysis and IR, NMR spectroscopy, individuality - by thin-layer chromatography. The synthesized compounds under the codes ПМП-4 - ПМП-6 were studied in an in vitro experiment for antimicrobial activity. All compounds exhibit pronounced antibacterial activity against the presented gram-positive and gram-negative test strains, in particular, they exhibit moderate activity against the gram-positive strain of Staphylococcus aureus ATCC 6538. The compound ПМП-6 exhibits moderate activity against gram-positive bacteria Bacillus subtilis and moderate antibacterial action against the gram-negative test strain Escherichia coli ATCC 25922. The compound ПМП-6 also has antifungal activity against the yeast fungus Candida albicans ATCC 10231.