SYNTHESIS AND ANTIBACTERIAL PROPERTIES OF N,N-DISUBSTITUTED β-AMINO ACIDS CONTAINING FUNCTIONALIZED THIAZOLE FRAGMENT IN THE STRUCTURE

E. Urbonavičiūtė, R. Vaickelionienė, G. Vaickelionis, V. Mickevičius

Abstract


Aminothiazoles were synthesized from the thioureido acid and halo carbonyl compounds by the Hantzsch method. The bromination of thiazolone, performed in acetic acid at 30 °C, gave the expected product 3-[(5,5-dibromo-4-oxo-4,5-dihydrothiazol-2-yl)(4-methoxyphenyl)amino]propanoic acid. The methylene group in the five-membered heterocyclic ring easily participates in condensation reactions with carbaldehydes. All these reactions were carried out in a mixture of water and 2-propanol in the presence of sodium carbonate. The formed sodium salts were converted into acids by acidifying the reaction mixture with acetic acid to pH 6. The 3-[{5-[4-{[2-[(2-carboxyethyl)-(4-methoxyphenyl)amino]-4-oxo-1,3-thiazol-5(4H)-ylidene]methyl}phenyl)methylidene]-4-oxo-4,5-dihydro-1,3-thiazol-2-yl]-(4-methoxyphenyl)-amino]propanoic acid was obtained analogously to the above-mentioned method, only instead of carbaldehyde using dialdehyde terephthalaldehyde.

The synthesized compounds 1-13 were evaluated for their antibacterial activity against the Xanthomonas campestris, Rhizobium radiobacter and Escherichia coli strains by the agar diffusion technique. Their activities were compared with those of the known antibacterial agent ampicillin (control C). The evaluation was performed at the Laboratory of Biotechnology of the Department of Organic Chemistry (Kaunas University of Technology). The growth of bacteria and the antibacterial activity were determined by using the Luria-Bertani (LB) nutrition media. The following concentrations of solutions in dimethyl sulfoxide were prepared: 1000, 500, 250, 125, 50 and 25 μg/ml. The prepared test-samples were incubated at 37 °C for 48 h. The effectiveness of the compounds was determined by measuring the zones of inhibition on a bacterial culture.

The test cultures of E. coli appeared not to be sensitive to any concentration of the tested compounds. Nine of the thirteen compounds were inactive against the Xanthomonas campestris bacterium strain, and only four of them – the condensed aminothiazole derivative 3-[(4-methoxyphenyl)-(4,5,6,7-tetrahydrobenzothiazol-2-yl)amino]propanoic acid (4) and thiazolone derivatives 3-[(5,5-dibromo-4-oxo-4,5-dihydrothiazol-2-yl)(4-methoxyphenyl)amino]propanoic acid (6), (Z)-3-[(5-(4-bromobenzylidene)-4-oxo-4,5-dihydrothiazol-2-yl)(4- methoxyphenyl)amino]propanoic acid (8), and (Z)-3-[(5-(4-chlorobenzylidene)-4-oxo-4,5-dihydro-thiazol-2-yl)(4- methoxyphenyl)amino]propanoic acid (9) at a concentration of 1000 μg/ml inhibited the growth of the X. campestris strain. It should be noted that compound 9 (at the same concentration) was also active against the Rh. radiobacter bacterium strain.

Hence, the results revealed the most effective compound – (Z)-3-[(5-(4-chlorobenzylidene)-4-oxo-4,5-dihydrothiazol-2-yl)(4-methoxyphenyl)amino]propanoic acid (9), which inhibited the growth of the Xanthomonas campestris and Rhizobium radiobacter bacteria strains.

DOI: http://dx.doi.org/10.5755/j01.ct.68.1.18877


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