Synthesis and hemostatic and antimicrobial activities of the sodium salts of N-acyl-5-bromo(3,5-dibromo)anthranilic acids

Abstract

Acylation of 5-bromo(3,5-dibromo)anthranilic acids with the corresponding anhydrides yielded 10 N-acyl-5-bromo(3,5-dibromo)anthranilic acids. The resulting compounds were reacted with 10% sodium hydroxide to convert them to the corresponding sodium salts. The hemostatic and antimicrobial activities against Staphylococcus aureus and Escherichia coli of the resulting compounds were studied. Compound IV, containing a phenyl residue in the acyl fragment, was found to have marked hemostatic activity (18.2%) and weak antimicrobial activity. The minimum inhibitory concentration for this compound was 500 mg/ml against S. aureus and E. coli. The other sodium salts were significantly less active.Key words: Sodium salts of N-acyl-5-bromo(3,5-dibromo)anthranilic acids, hemostatic and antimicrobial activities, synthesis.Anthranilic acid is known to take part in the biosynthesis of antibiotics [1], while the sodium salts of N-acylanthranilic acids have anti-inflammatory, antiproteolytic, and antimicrobial activities [2,3].We report here the synthesis of the sodium salts of N-acyl-5-bromo(3,5-dibromo)anthranilic acids [4] and studies of their hemostatic and antimicrobial actions.N-acyl-5-bromo(3,5-dibromo)anthranilic acids (I -IV, VI -X) were synthesized by acylation of 5-bromo-(3,5-dibromo)anthranilic acids with monocarboxylic acid anhydrides. Compound V was prepared by reaction with phthalic anhydride in ethyl acetate using a published method [5]; derivatives I and VIII were prepared in glacial acetic acid at room temperature; compound II was obtained in pyridine at 18°C. The calculated quantities of 10% NaOH were used to convert the compounds into their sodium salts; in the case of compound V, the disodium salt of N-phthalyl-5-bromoanthranilic acid was obtained.The sodium salts of compounds I -X were crystalline substances, white or white with a yellow tinge, soluble in water, ethanol, DMSO, and DMF. Structures were confirmed using their IR and 1 H NMR spectra (Table 1). EXPERIMENTAL CHEMICAL SECTIONThe 1 H NMR spectra of compounds I -X were recorded on a BS-567A spectrometer (working frequency 100 MHz) in DMSO-d 6 with HMDS as the internal standard; 1 H NMR spectra are given in Table 1. IR spectra were taken on a Specord M-80 spectrophotometer in Vaseline grease. Reaction courses and compound purities were monitored by TLC on Silufol UV-254 ® plates developed in acetone:chloroform (1:9); spots were detected with iodine vapor. The physicochemical properties of study compounds are shown in Table 1. Elemental analysis data for the compounds synthesized here were consistent with calculated values.N-Phthalyl-5-bromoanthranilic acid (V). A solution of 2.22 g (15 mmol) of phthalic anhydride in 10 ml of ethyl acetate was poured into a solution of 3.2 g (15 mmol) of 5-bromoanthranilic acid in 10 ml of ethyl acetate with mixing. The reaction mixture was kept for 24 h. The resulting precipitate was collected by filtration, dried, and recrystallized from a mixture of water and ethanol (2:1). The 12 0091-150X/11/4501-0012