Thiosemikarbazony a jejich antimykobakteriální účinky

English version

Autoři: Veronika Opletalová; Jan Doležel
Působiště autorů: Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Chemistry and Drug Analysis
Vyšlo v časopise: Čes. slov. Farm., 2013; 62, 78-83
Kategorie: Původní práce

Souhrn

Antimykobakteriální účinky thiosemikarbazonů byly objeveny ve druhé polovině čtyřicátých let 20. století. Nejznámějším zástupcem těchto sloučenin je thioacetazon používaný v terapii tuberkulózy od přelomu čtyřicátých a padesátých let. Pro závažné vedlejší účinky se dnes používá jen málokdy. Tato práce pojednává o antimykobakteriálních účincích thiosemikarbazonů a N,N-dimethylthiosemikarbazonů odvozených od 5-alkyl-2-acetylpyrazinů. Některé z těchto sloučenin významně inhibovaly růst Mycobacterium tuberculosis H₃₇Rv, ale pro svoji toxicitu nepostoupily do in vivo studií. Nicméně mohou být využity jako modelové sloučeniny pro studium mechanismů antimykobakteriálních účinků thiosemikarbazonů.

Klíčová slova:
tuberkulóza – thiosemikarbazony acetylpyrazinů – antimykobakteriální účinky

Zdroje

1. Cole S. T., Brosch R., Parkhill J., Garnier T., Churcher C., Harris D., Gordon S. V., Eiglmeier K., Gas S., Barry III C. E., Tekaia F., Badcock K., Basham D., Brown D., Chillingworth T., Connor R., Davies R., Devlin K., Fettwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K., Krogh A., McLean J., Moule S., Murphy L., Oliver K., Osborne J., Quail M. A., Rajandream M.-A., Rogers J., Rutter S., Seeger K., Skelton R., Squares R., Squares S., Sulston J. E., Taylor K., Whitehead S., Barrell B. G. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 1998; 393, 537–544.

2. Young D. B. Blueprint for the white plague. Nature 1998; 393, 515–516.

3. Tripathi R. P., Tewari N. T., Dwivedi N., Tiwari V. K. Fighting Tuberculosis: An old disease with new challenges. Med. Res. Rev. 2005; 25, 93–131.

4. Frieden T. R., Sterling T. R. Munsiff S. S., Watt C. J., Dye C. Tuberculosis. Lancet 2003; 362, 887–899.

5. World Health Organization. Global Tuberculosis Report 2012. http://www.who.int/tb/publications/global_report/en/ (11. 2. 2013)

6. Biava M., Porreta G. C., Deidda D., Pompei R. New trends in the development of antimycobacterial compounds. Infect. Disord.: Drug Targets 2006; 6, 159–182.

7. Kaufmann S. H. E. Tuberculosis and AIDS: A devilish liaison. Drug Discovery Today 2007; 12, 891–893.

8. Mukherjee J. S., Rich M. L., Socci A. R., Joseph J. K., Viru F. A., Shin S. S., Furin J. J., Becerra M. C., Barry D. J., Kim J. Y., Bayona J., Farmer P., Smith Fawzi M. C., Seung K. J. Programmes and principles in treatment of multidrug-resistant tuberculosis. Lancet 2004, 363, 474–481.

9. Kushwaha S. K., Shakya M. J. Protein interactions network analysis – Approach for potential drug target identification in Mycobacterium tuberculosis. J. Theor. Biol. 2010; 262, 284–294.

10. Minion J., Gallant V., Wolfe Y., Jamienson F., Long R. Multidrug and extensively drug resistant tuberculosis in Canada 1997–2008: Demographic and disease characteristics. PLoS One 2013; 8, e53466.

11. Donald P. R., van Helden P. D. The global burden of tuberculosis: Combating drug resistance in difficult times. N. Engl. J. Med. 2009, 360, 2393–2395.

12. Sensi P. History of development of rifampin. Rev. Infect. Dis. 1983; 5(Suppl. 3), S402–406.

13. Cohen, J. Approval of novel TB drug celebrated: With restraint. Science 2013; 339, 130.

14. Abu-Raddad, L. J., Sabatelli, L., Achtenberg, J. T., Sugimoto, J. D., Longini, I. M., Jr., Dye, C., Halloran, M. E. Epidemiological benefits of more-effective tuberculosis vaccines, drugs, and diagnostics. Proc. Natl. Acad. Sci. U. S. A. 2009; 106, 13980–13985.

15. Ginsberg A. M. Drugs in development for tuberculosis. Drugs 2010; 70, 2201–2214.

16. Ma Z., Lienhardt C., McIIIeron H., Nunn A. J., Wang X. Global tuberculosis drug development pipeline: The need and the reality. Lancet 2010; 375, 2100–2119.

17. Domagk G., Behnisch R., Mietzsch F., Schmidt H. Naturwissenschaften 1946; 33, 315.

18. Hantschman L., Werner R. Zu Kombinations Behandlung der Lungentuberkulose mit Conteben und PAS (Combined conteben and PAS therapy of pulmonary tuberculosis). Arztl. Wochensc. 1950; 5, 525–528.

19. Brecke F., Bohm, F. Zwei Jahre Conteben in Heilstätte (Two years´ sanatorium use of conteben). Hippokrates 1950; 21, 188–193.

20. Abate G., Koivula T., Hoffner S. E. In vitro activity on mycobacterial species belonging to the Mycobacterium tuberculosis complex. Int. J. Tuber. Lung Dis. 2002; 6, 933–935.

21. Bermudez L. F., Reynolds R., Kolonoski P., Aralar P., Inderlied C. B., Young L. S. Thiosemicarbazol (thiacetazone-like) compound with activity against Mycobacterium avium in mice. Antimicrob. Agents Chemother. 2003; 47, 2685–2687.

22. Bermudez L. F., Kolonoski P., Seitz L. E., Petrofsky M., Reynolds R., Wu M., Young L. S. SRI-268, a thiosemicarbazole, in combinatiom with mefloquine and moxifloxacin for treatment of murine Mycobacterium avium complex disease. Antimicrob. Agents Chemother. 2004; 48, 3556–3558.

23. Shahab F. M., Kobarfard F., Dadashzadeh S. Simultaneous determination of a new antituberculosis agent KBF-611 and its deacetylated metabolite in mouse and rabbit plasma by HPLC. Arch. Pharmacal Res. 2009; 32, 1453–1460.

24. Shahab F. M., Kobarfard F., Shafaghi B., Dadashzadeh S. Preclinical pharmacokinetics of KBF-611, a new antituberculosis agent in mice and rabbits, and comparison with thiacetazone. Xenobiotica 2010; 40, 225–234.

25. Kushner S., Dalalian H., Sanjurjo J. L., Bach F. L., Jr., Safir S. S., Smith V. K., Jr., Williams J. H. Experimental chemotherapy of tuberculosis. II. The synthesis of pyrazinamides and related compounds. J. Am. Chem. Soc. 1952; 74, 3617–3621.

26. Milczarska B., Foks H., Trapkowski Z., Milzynska-Kolaczek A., Janowiec M., Zwolska Z., Andrzejczyk Z. Studies on pyrazine derivatives. XXXII. Synthesis and tuberculostatic activity of acetylpyrazine thiosemicarbazone derivatives. Acta Pol. Pharm. 1998, 55, 289–295.

27. Opletalova V., Kalinowski D. S., Vejsova M., Kunes J., Pour M., Jampilek J., Buchta V., Richardson D. R. Identification and characterization of thiosemicarbazones with antifungal and antitumor effects: Iron chelation mediating cytotoxic activity. Chem. Res. Toxicol. 2008; 21, 1878–1889.

28. Collins L., Franzblau S. G. Microplate alamar blue assay versus BACTEC 460 system for high-throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium avium. Antimicrob. Agents Chemother. 1997; 41, 1004–1009.

29. Coxon G. D., Craig D., Corrales R. M., Vialla E., Gannoun-Zaki L. Synthesis, antitubercular activity and mechanism of resistance of highly effective thiacetazone analogues. PLoS One 2013; 8, e53162.

30. Qian L., Ortiz de Montellano P. R. Oxidative activation of thiacetazone by the Mycobacterium tuberculosis flavin monooxygenase EtaA and human human FMO1 and FMO3. Chem. Res. Toxicol. 2006; 19, 443–449.

31. Dover L. G., Alahari A., Gatraud P., Gomes J. M., Bhowruth V., Reynolds R. C., Besra G. S., Kremer L. EthA, a common activator of thiocarbamide-containing drugs acting on different mycobacterial targets. Antimicrob. Agents Chemother. 2007; 51, 1055–1063.

32. Francois A. A., Nishida C. R., Ortiz de Montellano P. R., Phillips I. R., Shephard E. A. Human flavin-containing monooxygenase 2.1 catalyzes oxygenation of antitubercular drugs thiacetazone and ethionamide. Drug Metab. Dispos. 2009; 37, 178–186.

33. Alahari A., Trivelli X., Guerardel Y., Dover L. G., Besra G. S., Sacchettini J. C., Reynolds R. C., Coxon G. D., Kremer L. Thiacetazone, an antitubercular drug that inhibits cyclopropanation of cell wall mycolic acids in mycobacteria. PLoS One 2007; 12, e1343.

34. Alahari A., Alibaud L., Trivelli X., Gupta R., Lamichhane G., Reynolds R. C., Bishai W. R., Guerardel Y., Kremer L. Mycolic acid methyltransferase, MmaA4, is necessary for thiacetazone susceptibility in Mycobacterium tuberculosis. Mol. Microbiol. 2009; 71, 1263–1277.

35. Banerjee D., Bhattacharyya R. Isoniazid and thioacetazon may exhibit antitubercular activity by binding directly with the active site of mycolic acid cyclopropane synthase: Hypothesis based on computational analysis. Bioinformation 2012; 8, 787–789.

36. Grzegorzewicz A. E., Korduláková J., Jones V., Born S. E., Belardinelli J. M., Vaquié A., Gundi V. A., Madacki J., Slama N., Laval F., Vaubourgeix J., Crew R. M., Gicquel B., Daffé M., Morbidoni H. R., Brennan P. J., Quémard A., McNeil M. R., Jackson M. A common mechanism of inhibition of the Mycobacterium tuberculosis mycolic acid biosynthetic pathways by isoxyl and thiacetazone. J. Biol. Chem. 2012; 287, 38434–38441.

37. Bellardinelli J. M., Morbidoni H. R. Mutations in the essential FAS II -hydroxyacyl ACP dehydratase complex confer resistance to thiacetazone in Mycobacterium tuberculosis and Mycobacterium kansasii. Mol. Microbiol. 2012; 86, 568–579.

38. Singh, V., Mani, I., Chaudhary, D. K., Somvanshi, P. The β-ketoacyl-ACP synthase from Mycobacterium tuberculosis as potential drug target. Curr. Med. Chem. 2011; 18, 1318–1324.

39. Rosado L. A., Caceres R. A., de Azevedo W. F., Jr., Basso L. A., Santos D. S. Role of serine 140 in the mode of action of Mycobacterium tuberculosis β-ketoacyl-ACP reductase (MabA). BMC Res. Notes 2012; 5, 526.

40. Cantaloube S., Veyron-Churlet R., Haddache N., Daffé M., Zerbib D. The Mycobacterium tuberculosis FAS-II dehydratases and methyltransferases define the specificity of the mycolic acid elongation complexes. PLoS One 2011; 6, e19564.

41. Arora P., Goyal A., Natarajan V. T., Rajacumara E., Verma P., Gupta R., Yousuf M., Trivedi O. A., Mohanty D., Tyagi A., Sankaranarayanan R., Gokhale R. S. Mechanistic and functional insight into fatty acid activation in Mycobacterium tuberculosis. Nat. Chem. Biol. 2009; 5, 166–173.

42. Mohanty D., Sankaranarayanan R., Gokhale R. S. Fatty acyl-AMP ligases and polyketides synthases are unique enzymes of lipid biosynthetic machinery in Mycobacterium tuberculosis. Tuberculosis 2011; 91, 448–455.

43. Duckworth B. P., Nelson K. M., Aldrich C. C. Adenylating enzymes in Mycobacterium tuberculosis as drug targets. Curr. Top. Med. Chem. 2012; 12, 766–796.