본문 바로가기
HOME> 논문 > 논문 검색상세

논문 상세정보

Synthesis and Biological Evaluations of Enoxacin Carboxamide Derivatives

Arayne, M.Saeed    (Department of Chemistry, University of Karachi   ); Sultana, Najma    (Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Karachi   ); Haroon, Urooj    (Department of Chemistry, University of Karachi   ); Mesaik, M.Ahmed    (Panjwani Center for Molecular Medicine and Drug Research (PCMD), International Centre for Biological and Chemical Sciences, University of Karachi   ); Asif, Muhammad    (Panjwani Center for Molecular Medicine and Drug Research (PCMD), International Centre for Biological and Chemical Sciences, University of Karachi  );
  • 초록

    The present work deals with the synthesis of various enoxacin analogues via nucleophilic substitution of 3- carboxylic acid moiety of the drug by aromatic amines. The free carboxylic group was utilized in the formation of amides and the effect of functional group exchange on different biological activities of the parent was evaluated. The structure of these derivatives was established by various spectroscopic techniques and mass spectrometry. The derivatives were evaluated as antibacterial agents against a series of Gram-positive and Gram-negative bacteria whereby some of them displayed considerably improved antimicrobial profile against Gram-negative test strains. Additionally unlike enoxacin, the derivatives were also found to modulate oxidative burst response of phagocytes exhibiting moderate to significant inhibitory activity.


  • 주제어

    Enoxacin .   Nucleophilic substitution .   Derivatives .   Antibacterial activity .   Oxidative burst response.  

  • 참고문헌 (36)

    1. Blandeau, J. M., Expanded activity and utility of the new fluoroquinolones: A review. Clini. Therap., 21, 3-40 (1999) 
    2. Chapman, J. S. and Georgopapadakou, N. H., Routes of quinolone permeation in Escherichia coli. Antimicrob. Chemother., 32, 438-442 (1988) 
    3. Foroumadi, A., Mansouri, S., Kiani, Z., and Rahmani, A., Synthesis and in vitro antibacterial evaluation of N-[5-(5-nitro-2-thienyl)-1, 3, 4-thiadiazole-2-yl]piperazinyl quinolones. Eur. J. Med. Chem., 38, 851-854 (2003) 
    4. Paton, J. H. and Reeves, D. S., Fluoroquinolone antibiotics. Microbiology, pharmacokinetics and clinical use. Drugs., 36, 193-228 (1988) 
    5. Sissi, C. and Palumbo, M., The quinolone family: From antibacterial to anticancer agents. Curr. Med. Chem.-Anti-Cancer Agents., 3, 439-450 (2003) 
    6. Tauber, S. C. and Nau, R., Immunomodulatory properties of antibiotics. Curr. Mol. Pharmacol., 1, 68-79 (2008) 
    7. Foroumadi, A., Emami, S., Mehni, M., Moshafi, M. H., and Shafiee, A., Synthesis and antibacterial activity of N-[2-(5-bromothiophen-2-yl)-2-oxoethyl] and N-[(2-5-bromothiophen-2-yl)-2-oximinoethyl] derivatives of piperazinyl quinolones. Bioorg. Med. Chem. Lett., 15, 4536-4539 (2005) 
    8. Lester, A. M., Bacterial topoisomerase inhibitors: Quinolone and pyridone antibacterial agents. Chem. Rev., 105, 559-592 (2005) 
    9. Li, Z. R., Guo, H. Y., and Zhang, Z. P., Studies on pyridone carboxylic acids as anti-bacterial agents. IX. Study on prodrugs of some pyridone carboxylic acids. Yao Xue Xue Bao., 26, 111-6 (1991) 
    10. Sanders, C. C., Ciprofloxacin: in vitro activity, mechanism of action, and resistance. Rev Infect Dis., 10, 516-527 (1988) 
    11. Wood, M. J., Tissue penetration and clinical efficacy of enoxacin in respiratory tract infections. Clin. Pharmacokinet., 16, 38-45 (1989) 
    12. Chu, D. T. W., Fernandes, P. B., Claiborne, A. K., Pihuleac, E., Nordeen., and Pernet, A. G., Synthesis and structureactivity relationships of novel arylfluoroquinolone antibacterial agents. J. Med. Chem., 28, 1558-1564 (1985) 
    13. Anderson, V. E. and Osheroff, N., Type II topoisomerases as targets for quinolone antibacterials: Turning Dr. Jekyll into Mr. Hyde. Curr. Pharmaceut. Design., 7, 339-355 (2001) 
    14. Koga, H., Itoh, A., Murayama, S., Suzue, S., and Irikura, T., Structure-activity relationships of antibacterial 6, 7-and 7, 8-disubstituted 1-alkyl-1, 4-dihydro-4-oxoquinoline-3-carboxylic acids. J. Med. Chem., 23, 1358-1363 (1980) 
    15. Helfand, S. L., Werkmeister, J., and Roder, J. C., Chemiluminescence response of human natural killer cells. I. The relationship between target cell binding, chemiluminescence, and cytolysis. J. Exp. Med., 156, 492-505 (1982) 
    16. Mascellino, M. T., Farinelli, S., Iegri, F., Iona, E., and De Simone, C., Antimicrobial activity of fluoroquinolones and other antibiotics on 1, 116 clinical Gram-positive and Gramnegative isolates. Drugs Expert. Clin. Res., 24, 139-151(1998) 
    17. Anacona, J. R. and Toledo, C., Synthesis and antibacterial activity of metal complexes of ciprofloxacin. Transi. Metal Chem., 26, 228-231 (2001) 
    18. Daniel, T. W. C. and Prabhavathi, B. F., Structure-activity relationships of the fluoroquinolones. Antimicrob. Chemother., 33, 131-135 (1989) 
    19. Janknegt, R., Fluorinated quinolones. A review of their mode of action, antimicrobial activity, pharmacokinetics and clinical efficacy. Pharm Weekbl [Sci]., 8, 1-21 (1986) 
    20. Pfeiffer, S., Lass, A., Schmidt, K., Mayer, B., Protein tyrosine nitration in mouse peritoneal macrophages activated in vitro and in vivo: evidence against an essential role of peroxynitrite. FASEB J., 15, 2355-64 (2001) 
    21. Chin, N. X. and Neu, H. C., In vitro activity of enoxacin, a quinolone carboxylic acid, compared with those of norfloxacin, new beta-lactams, aminoglycosides, and trimethoprim. Antimicrob. Chemother., 24, 754-763 (1983) 
    22. Domagala, J. M., Heifetz, C. L., Hutt, M. P., Mich, T. F., Nichols, J. B., Solomon, M., and Worth, D. F., 1-Substituted 7-[3-[(ethylamino) methyl]-1-pyrrolidinyl]-6, 8-difluoro-1, 4-dihydro-4-oxo-3-quinolinecarboxylic acids. New quantitative structure activity relationships at N1 for the quinolone antibacterials. J. Med. Chem., 31, 991-1001 (1988) 
    23. Ball, P., Fernald, A., and Tillotson, G., Therapeutic advances of new fluoroquinolones., Expert. Opin. Invest. Drugs., 7, 761-783 (1998) 
    24. Crumplin, G. C., Aspects of chemistry in the development of the 4-quinolone antibacterial agents. Clin. Infect. Dis. [Rev Infect Dis], 10, 1-9 (1988) 
    25. Foroumadi, A., Emami, S., Mansouri, S., Javidnia, A., Saeid-Adeli, N., Shirazi, F. H., and Shafiee, A., Synthesis and antibacterial activity of levofloxacin derivatives with certain bulky residues on piperazine ring. Eur. J. Med. Chem., 42, 985-992 (2007) 
    26. Ball, P., Quinolone-induced QT interval prolongation: a notso-unexpected class effect. J. Antimicrob. Chemother., 45, 557-559 (2000) 
    27. Foroumadi, A., Emami, S., Hassanzadeh, A., Rajaee, M., Sokhanvar, K., Moshafi, M. H., and Shafiee, A., Synthesis and antibacterial activity of N-(5-benzylthio-1, 3, 4-thiadiazol-2-yl) and N-(5-benzylsulfonyl-1, 3, 4-thiadiazol-2-yl) piperazinyl quinolone derivatives. Bioorg. Med. Chem. Lett., 15, 4488-4492(2005) 
    28. Lesher, G. Y., Froelich, E. J., Gruett, M. D., Bailey, J. H., and Brundage, R. P., 1,8-Naphthyridine Derivatives. A New Class of Chemotherapeutic Agents. J. Med. Pharm. Chem., 5, 1063-1065 (1962) 
    29. Bauer, A. W., Kirby, W. M. M., Sherris, J. C., and Turck, M., Antibiotic susceptibility testing by a standard single disk method. Am. J. Clin. Pathol., 45, 493-496 (1966) 
    30. Klopman, G., Macina, O. T., Levinson, M. E., and Rosenkranz, H. S., Computer automated structure evaluation of quinolone antibacterial agents. Antimicrob. Agents Chemother., 31, 1831-1840 (1987) 
    31. Shen, L. L., Mitscher, L. A., Sharma, P. N., O'Donnell, T. J., Chu, D. W. T., Cooper, C. S., Rosen, T., and Pernet, A. G., Mechanism of inhibition of DNA gyrase by quinolone antibacterials: A cooperative drug-DNA binding model. Biochemistry., 28, 3886-3894 (1989) 
    32. Wiik, P., Opstad, P. K., Boyum, A., Granulocyte chemiluminescence response to serum opsonized zymosan particlesex vivo during long-term strenuous exercise, energy and sleep deprivation in humans. Eur. J. Appl. Physiol., 73, 251-258 (1996) 
    33. Turnidge, J., Pharmacokinetics and pharmacodynamics of fluoroquinolones. Drugs., 58, 29-36 (1999) 
    34. Franklin, V., Tamara, Z., Carlos, R., Alvaro, R., Tulynan. C., Yrene, D., Carla, I., Ylec, M. C., Ver$\acute{o}$nica, L., Lubimar, G., Jessenia, O., and Alberto, F., Synthesis, primary photophysical and antibacterial properties of naphthyl ester cinoxacin and nalidixic acid derivatives. J. Photochem. Photobiol. B: Biol., 92, 83-90 (2008) 
    35. Hirosato, K., Fumio, S., Kiyotaka, K., and Goro, T., Studies on prodrugs. 7. Synthesis and antimicrobial activity of 3-formylquinolone derivatives. J. Med. Chem., 31, 221-225 (1988) 
    36. Tomi$\check{s}$ic, Z. B., Kujund$\check{z}$ic, N., Krajacic, M. B., Vi$\check{s}$njevac, A., and Kojic-Prodic, B., Molecular structures of new ciprofloxacin derivatives. J. Mol. Struct., 611, 73-81 (2002) 
  • 이 논문을 인용한 문헌 (2)

    1. 2010. "" Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea, 33(12): 1901~1909     
    2. 2011. "" Bulletin of the Korean Chemical Society, 32(2): 483~488     

 활용도 분석

  • 상세보기

    amChart 영역
  • 원문보기

    amChart 영역

원문보기

무료다운로드
  • 원문이 없습니다.
유료다운로드

유료 다운로드의 경우 해당 사이트의 정책에 따라 신규 회원가입, 로그인, 유료 구매 등이 필요할 수 있습니다. 해당 사이트에서 발생하는 귀하의 모든 정보활동은 NDSL의 서비스 정책과 무관합니다.

원문복사신청을 하시면, 일부 해외 인쇄학술지의 경우 외국학술지지원센터(FRIC)에서
무료 원문복사 서비스를 제공합니다.

NDSL에서는 해당 원문을 복사서비스하고 있습니다. 위의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.

이 논문과 함께 출판된 논문 + 더보기