Synthesis, Antimicrobial Activities of New Sulfonamidobenzoxazoles and Molecular Docking Studies on Escherichia coli TEM-1 β-Lactamase

Tugba Ertan-Bolelli, Kayhan Bolelli, Suzan Okten, Fatma Kaynak-Onurdag, Esin Aki-Yalcin, Ismail Yalcin
2017 Croatica Chemica Acta  
β-Lactam antibiotics are frequently used for treatment of multi-drug resistant microbial infections and the most common mechanism of resistance against these antibiotics is bacterial β-lactamase production. Herein, we reported the design, synthesis and in vitro antimicrobial activities of some new 2-substituted-5-(2,4-dinitrophenylsulfonamido)benzoxazole derivatives. Compounds TN1, TN2, and TN3 were found to be significantly active against E. coli isolate which contains extended spectrum
more » ... ded spectrum β-lactamase enzyme at the MIC value of 8 µg mL -1 and that is 4-fold higher than the reference drug ampicillin. We performed molecular docking studies into active site of Escherichia coli TEM-1 β-lactamase enzyme in order to predict the protein-ligand interactions. According to the docking results, compounds TN1, TN2, and TN3 showed strong interactions between the important active site residues which are responsible for the catalytic mechanism of TEM-1 β-lactamase enzyme and a good correlation is found with the experimental data. All of the solvents and chemicals were purchased from commercial vendors and were used without purification. The melting points were uncorrected and measured on Buchi B540. FTIR spectra were obtained on a Agilent Technologies Cary 630 FTIR spectrometer. 1 H NMR and 13 C NMR spectra were obtained on a VARIAN Mercury 400 MHz FT spectrometer, chemical shifts were expressed as ppm, and coupling constants (J) were expressed as hertz. Mass spectra were obtained on a Waters Micromass ZQ using the ESI method. Analytical data were obtained on elemental analyzer system Leco CHNS-932 CHNS-O analyzer and the results (C, H, N, S) were found within ± 0.4 % of the calculated amounts. GENERAL PROCEDURE FOR THE SYNTHESIS OF 5-(2,4-DINITROPHENYLSULFONAMIDO)BENZOXAZOLE DERIVATIVES (TN1-14) Firstly, 2-(4-substitutedphenyl)-5-aminobenzoxazole were prepared according to literature data. [14][15][16] Then 0.95 mmol pyridine and 0.52 mmol 2,4-dinitrobenzene-sulfonyl chloride (d) added to a solution of 0.048 mmol 2-(4-substitutedphenyl)-5-aminobenzoxazole in 2 mL dichloromethane. The reaction mixture was stirred for 16 hours at the room temperature. At the end of the reaction, the solid product was filtered and washed with saturated solution of CuSO4 and NaHCO3 in water, then recrystallized from ethyl acetate/n-hexan (1 : 4) mixture. [16, 17] All of the compounds are new. 2-PHENYL-5-(2,4-DINITROPHENYLSULFON- AMIDO)BENZOXAZOLE (TN1) 32 % yield; m.p 223-224 °C; IR max 3337,
doi:10.5562/cca3111 fatcat:2ce3mau4qvb45c5qtr4ouvt5um