Synthesis and antimicrobial activity of N-alkyl and N-aryl piperazine derivatives.

A series of substituted piperazine derivatives have been synthesized and tested for antimicrobial activity. The antibacterial activity was tested against Staphylococcus aureus (MTCCB 737), Pseudomonas aeruginosa (MTCCB 741), Streptomyces epidermidis (MTCCB 1824) and Escherichia coli (MTCCB 1652), and antifungal activity against Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger. All synthesized compounds showed significant activity against bacterial strains but were found to be less active against tested fungi. In vitro toxicity tests demonstrated that compounds 4d and 6a showed very less toxicity against human erythrocytes.

[1]  K. Rossen,et al.  Highly diastereoselective reaction of a chiral, non-racemic amide enolate with (S)-glycidyl tosylate. Synthesis of the orally active HIV-1 protease inhibitor L-735,524 , 1994 .

[2]  J. Šubík,et al.  Fluconazole and itraconazole susceptibility of vaginal yeast isolates from Slovakia , 2004, Mycopathologia.

[3]  K. Rossen,et al.  Asymmetric hydrogenation of tetrahydropyrazines: Synthesis of (S)-piperazine-2-tert-butylcarboxamide, an intermediate in the preparation of the HIV protease inhibitor indinavir , 1995 .

[4]  F. Peypoux,et al.  Interactions of antibiotics of the iturin group with human erythrocytes. , 1986, Biochimica et biophysica acta.

[5]  Ellen Jo Baron,et al.  Manual of clinical microbiology , 1975 .

[6]  Y. Reilly,et al.  (S)-N-tert-butyl-3-(4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide [(S)-WAY-100135]: a selective antagonist at presynaptic and postsynaptic 5-HT1A receptors. , 1993, Journal of medicinal chemistry.

[7]  He Zhao,et al.  Indoline and piperazine containing derivatives as a novel class of mixed D(2)/D(4) receptor antagonists. Part 2: asymmetric synthesis and biological evaluation. , 2002, Bioorganic & medicinal chemistry letters.

[8]  S. J. Brickner,et al.  Synthesis and antibacterial activity of U-100592 and U-100766, two oxazolidinone antibacterial agents for the potential treatment of multidrug-resistant gram-positive bacterial infections. , 1996, Journal of medicinal chemistry.

[9]  J. Sobel,et al.  Nosocomial acquisition of Candida albicans: an epidemiologic study. , 1993, The Journal of infectious diseases.

[10]  P. Ball.  Quinolone generations: natural history or natural selection? , 2000, The Journal of antimicrobial chemotherapy.

[11]  G. Sharma,et al.  Studies on antimycotic properties of Datura metel. , 2002, Journal of ethnopharmacology.

[12]  T. Grasela,et al.  Prospective Surveillance of Intravenous Amphotericin B Use Patterns , 1990, Pharmacotherapy.

[13]  J. Kehne,et al.  5-Aryl-3-(alkylthio)-4H-1,2,4-triazoles as selective antagonists of strychnine-induced convulsions and potential antispastic agents. , 1994, Journal of medicinal chemistry.

[14]  R. D. Dyer,et al.  Design of 5-(3,5-di-tert-butyl-4-hydroxyphenyl)-1,3,4-thiadiazoles, -1,3,4-oxadiazoles, and -1,2,4-triazoles as orally-active, nonulcerogenic antiinflammatory agents. , 1993, Journal of medicinal chemistry.

[15]  C. Sergheraert,et al.  Synthesis and in vitro and in vivo antimalarial activity of N1-(7-chloro-4-quinolyl)-1,4-bis(3-aminopropyl)piperazine derivatives. , 2003, Journal of medicinal chemistry.

[16]  P. Darke,et al.  L-735,524: the design of a potent and orally bioavailable HIV protease inhibitor. , 1994, Journal of medicinal chemistry.

[17]  R. Chandra,et al.  Optically active antifungal azoles: synthesis and antifungal activity of (2R,3S)-2-(2,4-difluorophenyl)-3-(5-[2-[4-aryl-piperazin-1-yl]-ethyl]-tetrazol-2-yl/1-yl)-1-[1,2,4]-triazol-1-yl-butan-2-ol. , 2004, Bioorganic & medicinal chemistry.

[18]  P. Nyirjesy,et al.  Fluconazole Susceptibility of Vaginal Isolates Obtained from Women with Complicated Candida Vaginitis: Clinical Implications , 2003, Antimicrobial Agents and Chemotherapy.

[19]  A. Katritzky,et al.  The chemistry of N-substituted benzotriazoles. Part 14. Novel routes to secondary and tertiary amines and to N, N-disubstituted hydroxylamines , 1989 .

[20]  R. Egan,et al.  Acid degradation of erythromycin A and erythromycin B , 1971, Experientia.

[21]  D. W. Smith,et al.  Synthesis and biological evaluation of 1-(1,2-benzisothiazol-3-yl)- and (1,2-benzisoxazol-3-yl)piperazine derivatives as potential antipsychotic agents. , 1986, Journal of Medicinal Chemistry.

[22]  B. E. Evans,et al.  Cycloalkylpiperazines as HIV-1 protease inhibitors: enhanced oral absorption , 1995 .

[23]  J. Barbosa,et al.  Acid-base behavior of quinolones in aqueous acetonitrile mixtures. , 1997, Acta chemica Scandinavica.

[24]  R. Dabur,et al.  A fraction from Escherichia coli with anti-Aspergillus properties. , 2005, Journal of medical microbiology.

[25]  P. Appelbaum,et al.  The fluoroquinolone antibacterials: past, present and future perspectives. , 2000, International journal of antimicrobial agents.

[26]  Y. Mizuki,et al.  Pharmacokinetic interactions related to the chemical structures of fluoroquinolones. , 1996, The Journal of antimicrobial chemotherapy.

[27]  V. Fanos,et al.  Amphotericin B-Induced Nephrotoxicity: A Review , 2000, Journal of chemotherapy.

[28]  J. Kane,et al.  2,4-Dihydro-3H-1,2,4-triazole-3-thiones as potential antidepressant agents. , 1988, Journal of medicinal chemistry.

[29]  M. Kimura,et al.  Novel diphenylalkyl piperazine derivatives with dual calcium antagonistic and antioxidative activities. , 2002, Bioorganic & medicinal chemistry letters.

[30]  S. Piscitelli,et al.  Clinical pharmacology of systemic antifungal agents: a comprehensive review of agents in clinical use, current investigational compounds, and putative targets for antifungal drug development. , 1998, Advances in pharmacology.

[31]  C. Dence,et al.  FORMATION OF PHENYLPIPERAZINES BY A NOVEL ALUMINA SUPPORTED BIS-ALKYLATION , 1996 .

[32]  R. D. Dyer,et al.  1,3,4-Oxadiazole, 1,3,4-thiadiazole, and 1,2,4-triazole analogs of the fenamates: in vitro inhibition of cyclooxygenase and 5-lipoxygenase activities. , 1993, Journal of medicinal chemistry.

[33]  A. Katritzky,et al.  Properties and Synthetic Utility of N-Substituted Benzotriazoles. , 1998, Chemical reviews.

[34]  P. Darke,et al.  L-735,524: an orally bioavailable human immunodeficiency virus type 1 protease inhibitor. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[35]  J. Remington,et al.  Current Clinical Topics in Infectious Diseases , 1980 .

[36]  G. Kaatz,et al.  Structural features of piperazinyl-linked ciprofloxacin dimers required for activity against drug-resistant strains of Staphylococcus aureus. , 2003, Bioorganic & medicinal chemistry letters.

[37]  A. Katritzky,et al.  Syntheses of optically active tetrahydro-1H-pyrrolo[1,2-a]imidazol-2-ones and hexahydroimidazo[1,2-a]pyridin-2(3H)-ones. , 2002, Journal of Organic Chemistry.