Synthesis and Structure-Activity Relationship Analysis of Enamines as Potential Antibacterial Agents

Twenty-four new enamines [(Z)-4–15 and (E)-4–15] were synthesized for the first time. Their chemical structures were determined by means of 1H NMR spectroscopy, electrospray ionization-mass spectrometry, and elemental analysis. All of the compounds were assayed for antibacterial (Bacillus subtilis ATCC 6633, Escherichia coli ATCC 35218, Pseudomonas fluorescens ATCC 13525, and Staphylococcus aureus ATCC 6538) and antifungal (Aspergillus niger ATCC 16404, Candida albicans ATCC 10231, and Trichophyton rubrum ATCC 10218) activities by the 3-(4,5-dimethyl thiazole-2yl)-2,5-diphenyl tetrazolium bromide (MTT) method. Four compounds, (E)-ethyl 3-(4-fluorophenylamino)-2-(3-methoxyphenyl)acrylate ((E)-6), (E)-ethyl 3-(4-chlorophenylamino)-2-(3-methoxyphenyl)acrylate ((E)-9), (E)-ethyl 3-(4-bromophenylamino)-2-(3-methoxyphenyl)acrylate ((E)-12), and (E)-ethyl 3-(2,4-dibromophenylamino)-2-(3-methoxyphenyl)acrylate ((E)-13) showed considerable antibacterial activity against Pseudomonas fluorescens with minimum inhibitory concentrations of 12.5, 12.5, 3.12, and 6.25 μg mL–1, respectively. Structure–activity relationship analyses revealed that, in general, an (E)-isomer exhibited higher antibacterial activity than the corresponding (Z)-isomer.

[1]  P. la Colla,et al.  Synthesis and biological evaluation of benzo[d]isothiazole, benzothiazole and thiazole Schiff bases. , 2003, Bioorganic & medicinal chemistry.

[2]  Varma Rs,et al.  Isatin-3-anils as excystment and cysticidal agents against Schizopyrenus russelli. , 1975 .

[3]  S. Geib,et al.  Enantioselective Robinson annulation: synthesis of (+)-O-methyljoubertiamine , 1989 .

[4]  Varma Rs,et al.  Synthesis and antiviral and antibacterial activity of certain N-dialkylaminomethylisatin beta-thiosemicarbazones. , 1967 .

[5]  D. Sriram,et al.  Synthesis, Antibacterial, Antifungal, and Anti-HIV Evaluation of Norfloxacin Mannich Bases. , 2010 .

[6]  A. Ayscough,et al.  Structure-activity relationships of the peptide deformylase inhibitor BB-3497: modification of the methylene spacer and the P1' side chain. , 2003, Bioorganic & medicinal chemistry letters.

[7]  M. Brookhart,et al.  Lewis Acid-Catalyzed Synthesis of Aziridines , 1996 .

[8]  A. V. Shindikar,et al.  Novel fluoroquinolones: design, synthesis, and in vivo activity in mice against Mycobacterium tuberculosis H37Rv. , 2005, Bioorganic & medicinal chemistry letters.

[9]  Yunfei Du,et al.  Synthesis of N-substituted indole derivatives via PIFA-mediated intramolecular cyclization. , 2006, Organic letters.

[10]  E. Beccalli,et al.  Oxidation of 4-aryl-substituted isoxazolin-5-ones. A new synthesis of 2,5-diaryl-1,3-oxazin-6-ones , 1984 .

[11]  Y. Matsumoto,et al.  Anti-Helicobacter pylori agents. 4. 2-(Substituted guanidino)-4-phenylthiazoles and some structurally rigid derivatives. , 2000, Journal of medicinal chemistry.

[12]  H. Ge,et al.  Synthesis and antimicrobial activities of Schiff bases derived from 5-chloro-salicylaldehyde. , 2007, European journal of medicinal chemistry.

[13]  P. Yogeeswari,et al.  Synthesis and Screening for Anti-HIV Activity of Some N-Mannich Bases of Isatin Derivatives , 1999, Chemotherapy.

[14]  J. Donnelly,et al.  Comparison of NCCLS and 3-(4,5-Dimethyl-2-Thiazyl)-2,5-Diphenyl-2H-Tetrazolium Bromide (MTT) Methods of In Vitro Susceptibility Testing of Filamentous Fungi and Development of a New Simplified Method , 2000, Journal of Clinical Microbiology.

[15]  Zhu-Ping Xiao,et al.  Synthesis, structure, and structure-activity relationship analysis of enamines as potential antibacterials. , 2007, Bioorganic & medicinal chemistry.

[16]  Shijun Ren,et al.  Synthesis, biological evaluation, and quantitative structure-activity relationship analysis of new Schiff bases of hydroxysemicarbazide as potential antitumor agents. , 2002, Journal of medicinal chemistry.