Pohľad na perchlozón, antituberkulotikum z Ruskej federácie

Stiahnuť PDF English version

Autori: Ivan Malík ^1,2; Jozef Čižmárik ³; Mária Pecháčová ³
Pôsobisko autorov: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University in Bratislava Odbojárov 10, 832 32 Bratislava, Slovak Republic ¹; Institute of Chemistry, Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Slovak Medical University in Bratislava, Limbová 12, 833 03 Bratislava, Slovak Republic e-mail: malik@fpharm. uniba. sk ²; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University in Bratislava, Slovak Republic ³
Vyšlo v časopise: Čes. slov. Farm., 2020; 69, 203-210
Kategória: Přehledový článek

Súhrn

Prevalencia multirezistentnej tuberkulózy (multidrug-resistant tuberculosis – MDR-TB) a extenzívne rezistentnej tuberkulózy (extensively drug-resistant tuberculosis – XDR-TB) sa vo svete alarmujúcim tempom zvyšuje. Aktuálne programy „Boja proti tuberkulóze“ sú v Ruskej federácii podporované štátnou vládou, regionálnymi vládami a tiež zdravotníckymi inštitúciami. Každý región tento krajiny má však vlastné špecifiká a vyžaduje si špecifické intervencie. Napriek tomu, že niektoré nové antituberkuloticky (anti-TB) pôsobiace liečivá (bedachilín, delamanid) boli už relevantnými inštitúciami schválené a iné sľubné zlúčeniny, najmä zo skupiny oxazolidinónov, sú v rôznych fázach klinických hodnotení prebiehajúcich vo svete, nájdenie efektívnych, bezpečných, farmakokineticky výhodných, ekonomicky a logisticky dostupných anti-TB-liečiv stále zostáva pre medicínske a farmaceutické vedy veľkou výzvou. Tiosemikarbazónové liečivo perchlozón bolo v Ruskej federácii schválené v roku 2012 pre liečbu (samostatne, alebo ako aktívna zložka komplexných liečebných režimov) HIV-1-negatívnych a tiež HIV--1-pozitívnych pacientov, ktorí sú postihnutí MDR-TB alebo XDR-TB. Mechanizmus anti-TB-účinku perchlozónu by mohol byť podobný tomu, akým pôsobí tiacetazón, ktorý patrí do identickej chemickej skupiny. Perchlozóm musí byť pravdepodobne aktivovaný mykobakteriálne kódovanou oxygenázou (EthA) na reaktívne entity. Tieto aktívne formy by mohli pôsobiť viacerými mechanizmami, vrátane inhibície syntézy bunkovej steny mykobaktérií (kvôli interferencii s procesom dehydratácie syntázy mastných kyselín typu II) alebo senzitizácie bunky Mycobacterium tuberculosis voči oxidačnému stresu. V rámci relevantných predklinických a klinických štúdií perchlozónu boli potvrdené jeho výhodné farmakokinetické vlastnosti a tiež tolerovateľnosť ľudským organizmom. Aktuálne predbežné zistenia in vivo (animálne modely) by však mohli indikovať genotoxicitu po subakútnej inhalácii tohto liečiva. Z uvedeného dôvodu je veľmi žiaduce uvažovať o ďalšom vývoji výhodnejších spôsobov podania perchlozónu, ktoré sú založené na nano- a mikročasticových systémoch. Tieto inovatívne alternatívy by potenciálne zlepšili cielené dodanie liečiva, jeho účinnosť a znížili (eliminovali) by aj eventuálnu toxicitu.

Klíčová slova:

perchlozón – Mycobacterium tuberculosis – rezistencia – MDR-TB – XDR-TB – koinfekcia HIV-1

Zdroje

1. Vasava M. S., Bhoi M. N., Rathwa S. K., Borad M. A., Nair S. G., Patel H. D. Drug development against tuberculosis: Past, present and future. Indian J. Tuberc. 2017; 64, 252–275. doi: 10.1016/j.ijtb.2017.03.002

2. Hershkovitz I., Donoghue H. D., Minnikin D. E., May H., Lee O. Y., Feldman M., Galili E., Spigelman M., Rothschild B. M., Bar-Gal G. K. Tuberculosis origin: the Neolithic scenario. Tuberculosis 2015; 95(Suppl. 1), S122–S126. doi: 10.1016/j.tube.2015.02.021

3. World Health Organization (WHO). Global Tuberculosis Report 2019. Geneva: World Health Organization 2019; 297.

4. Chetty S., Ramesh M., Singh-Pillay A., Soliman M. E. S. Recent advancements in the development of anti-tuberculosis drugs. Bioorg. Med. Chem. Lett. 2017; 27, 370–386. doi: 10.1016/j.bmcl.2016.11.084

5. Koch A., Cox H., Mizrahi V. Drug-resistant tuberculosis: Challenges and opportunities for diagnosis and treatment. Curr. Opin. Pharmacol. 2018; 42, 7–15. doi: 10.1016/j.coph.2018.05.013

6. Mase S. R., Chorba T. Treatment of drug-resistant tuberculosis. Clin. Chest Med. 2019; 40, 775–795. doi: 10.1016/j.ccm.2019.08.002

7. Tiberi S., Zumla A., Battista Migliori G. Multidrug and extensively drug-resistant tuberculosis. Epidemiology, clinical features, management and treatment. Infect. Dis. Clin. North. Am. 2019; 33, 1063–1085. doi: 10.1016/j.idc.2019.09.002

8. Dadu M., Hovhannesyan A., Ahmedov S., van der Werf M. J., Dara M. Drug-resistant tuberculosis in Eastern Europe and Central Asia: a time-series analysis of routine surveillance data. Lancet Infect. Dis. 2020; 20, 250–258. doi: 10.1016/S1473-3099(19)30568-7

9. Belyaeva E., Chernokhaeva I., Sapozhnikova N., Nazarenko M., Starshinova A., Yablonskiy P. Factors predisposing to the development of extensive drug resistance of Mycobacterium tuberculosis. Medicinal Alliance (Medicinskiy Alyans; In Russian) 2017; 5, 51–56.

10. Ergeshov А. Е. Tuberculosis in the Russian Federation: Situation, challenges and perspectives. Annals of the Russian Academy of Medical Sciences (Vestnik RAMN; In Russian) 2018; 73, 330–337. doi: 10.15690/vramn1023

11. Meshkov I., Petrenko T., Keiser O., Estill J., Revyakina O., Felker I., Raviglione M. C., Krasnov V., Schartz Y. Variations in tuberculosis prevalence, Russian Federation: a multivariate approach. Bull. World Health Organ 2019; 97, 737–745. doi: 10.2471/BLT.19.229997

12. Yablonskii P. K., Vizel A. A., Galkin V. B., Shulgina M. V. Tuberculosis in Russia. Its history and its status today. Am. J. Respir. Crit. Care Med. 2015; 191, 372–376. doi: 10.1164/rccm.201305-0926OE

13. Augustynowicz-Kopeć E., Demkow U., Grzelewska--Rzymowska I., Korzeniewska-Koseła M., Langfort R., Michałowska-Mitczuk D., Rowińska-Zakrzewska E., Zielonka T. M., Ziołkowski J., Zwolska Z. Guidelines of Polish Respiratory Society concerning diagnosis, treatment and prevention of tuberculosis in adults and in children. Pneumol. Alergol. Pol. 2013; 81, 323–379.

14. Zellweger J.-P. Current options for the management of multi‑drug-resistant tuberculosis (review). Medicinal Alliance (Medicinskiy Alyans; In Russian) 2017; 6, 22–28.

15. Ryan N. J., Lo J. H. Delamanid: First global approval. Drugs 2014; 74, 1041–1045. doi: 10.1007/s40265-014-0241-5

16. Keam S. J. Pretomanid: First approval. Drugs 2019; 79, 1797–1803. doi: 10.1007/s40265-019-01207-9

17. Esposito S., Bianchini S., Blasi F. Bedaquiline and delamanid in tuberculosis. Expert Opin. Pharmacother. 2015; 16, 2319–2330. doi: 10.1517/14656566.2015.1080240

18. Sensi P. History of the development of rifampin. Rev. Infect. Dis. 1983; 5(Suppl. 3), S402–S406. doi: 10.1093/clinids/5.supplement_3.s402

19. Deltyba^® (delamanid) approved in Russian Federation for treatment of pulmonary multidrug-resistant tuberculosis (MDR-TB). https://www.otsuka.co.jp/en/company/newsreleases/2020/ 20200525_1.html (20.9.2020)

20. Haagsma A. C., Podasca I., Koul A., Andries K., Guillemont J., Lill H., Bald D. Probing the interaction of the diarylquinoline TMC207 with its target mycobacterial ATP synthase. PLoS One 2011; 6, art. no. e23575 (7 pp.). doi: 10.1371/journal.pone.0023575

21. Hards K., Robson J. R., Berney M., Shaw L., Bald D., Koul A., Andries K., Cook G. M. Bactericidal mode of action of bedaquiline. J. Antimicrob. Chemother. 2015; 70, 2028–2037. doi: 10.1093/jac/dkv05

22. Sarathy J. P., Gruber G., Dick T. Re-understanding the mechanisms of action of the anti-mycobacterial drug bedaquiline. Antibiotics (Basel) 2019; 8, art. no. 261 (12 pp.). doi: 10.3390/antibiotics8040261

23. Alahari A., Trivelli X., Guérardel 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; 2, art. no. e1343 (12 pp.). doi: 10.1371/journal.pone.0001343.

24. Xavier A. S., Lakshmanan M. Delamanid: A new armor in combating drug-resistant tuberculosis. J. Pharmacol. Pharmacother. 2014; 5, 222–224. doi: 10.4103/0976-500X.136121

25. Stover C. K., Warrener P., van Devanter D. R., Sherman D. R., Arain T. M., Langhorne M. H., Anderson S. W., Towell J. A., Yuan Y., McMurray D. N., Kreiswirth B. N., Barry C. E., Baker W. R. A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis. Nature 2000; 405, 962–966. doi: 10.1038/35016103

26. Baptista R., Fazakerley D. M., Beckmann M., Baillie L., Mur L. A. J. Untargeted metabolomics reveals a new mode of action of pretomanid (PA-824). Sci. Rep. 2018; 8, art. no. 5084 (7 pp.). doi: 10.1038/s41598-018-23110-1

27. Conradie F., Diacon A. H., Ngubane N., Howell P., Everitt D., Crook A. M., Mendel C. M., Egizi E., Moreira J., Timm J., McHugh T. D., Wills G., Bateson A., Hunt R., van Niekerk Ch., Li M., Olugbosi M., Spigelman M., on behalf of Nix-TB Trial Team. Bedaquiline, pretomanid and linezolid for treatment of extensively drug resistant, intolerant or non-responsive multidrug resistant pulmonary tuberculosis. N. Engl. J. Med. 2020; 382, 893–902. doi: 10.1056/NEJMoa1901814

28. Reddy Tetali S., Kunapaeddi E., Prasad Mailavaram R., Singh V., Borah P., Deb P. K., Venugopala K. N., Hourani W., Tekade R. K. Current advances in the clinical development of anti-tubercular agents. Tuberculosis 2020; 125, art. no. 101989 (12 pp.). doi: 10.1016/j.tube.2020.101989

29. Schrager L. K., Vekemens J., Drager N., Lewinsohn D. M., Olesen O. F. The status of tuberculosis vaccine development. Lancet Infect. Dis. 2020; 20, 28–37. doi: 10.1016/S1473-3099(19)30625-5

30. Pavlova M., Vinogradova T., Starshinova A., Sapozhnikova N., Chernokhaeva I., Archakova L., Yablonskii P. Confirmation of preclinical studies data on thioureidoiminomethylpyridinium perchlorate (perchlozon) in clinic. Int. J. Curr. Res. 2015; 7, 14501–14505.

31. Opletalová V., Doležel J. Thiosemicarbazones and their antimycobacterial effects. Čes. slov. Farm. 2013; 62, 78–83.

32. Pavan F. R., da Silva Maia P. I., Leite S. R. A., Deflon V. M., Batista A. A., Sato D. N., Franzblau S. G., Leite C. Q. F. Thiosemicarbazones, semicarbazones, dithiocarbazates and hydrazide/hydrazones: anti-Mycobacterium tuberculosis activity and cytotoxicity. Eur. J. Med. Chem. 2010; 45, 1898–1905. doi: 10.1016/j.ejmech.2010.01.028

33. Smolentsev A. I., Lavrenova L. G., Elokhina V. N., Nakhmanovich A. S., Larina L. L. Crystal structure of pyridine-4-aldehyde thiosemicarbazone perchlorate and trifluoromethane sulfonate. J. Struct. Chem. 2009; 50, 500–504. doi: 10.1007/s10947-009-0076-1

34. Volynets G. P., Tukalo M. A., Bdzhola V. G., Derkach N. M., Gumeniuk M. I., Tarnavskiy S. S., Starosyla S. A., Yarmoluk S. M. Benzaldehyde thiosemicarbazone derivatives against replicating and nonreplicating Mycobacterium tuberculosis. J. Antibiot. (Tokyo) 2019; 72, 218–224. doi: 10.1038/s41429-019-0140-9

35. Dover L. G., Alahari A., Gratraud P., Gomes J. M., Bhowruth V. E. EthA, a common activator of thiocarbamide-containing drugs acting on different mycobacterial targets. Antimicrob. Agents Chemother. 2007; 51, 1055–1063. doi: 10.1128/AAC.01063-06

36. Grzegorzewicz A. E., Eynard N., Quémard A., North E. J., Margolis A., Lindenberger J. J., Jones V., Korduláková J., Brennan P. J., Lee R. E., Ronning D. R., McNeil M. R., Jackson M. Covalent modification of the Mycobacterium tuberculosis FAS-II dehydratase by Isoxyl and Thiacetazone. ACS Infect. Dis. 2015; 1, 91–97. doi: 10.1021/id500032q

37. Qian L., Ortiz de Montellano P. R. Oxidative activation of thiacetazone by the Mycobacterium tuberculosis flavin monooxygenase EtaA and human FMO1 and FMO3. Chem. Res. Toxicol. 2006; 19, 443–449. doi: 10.1021/tx050328b

38. Vinogradova T. I., Zabolotnykh N. V., Vasilyeva S. N., Vitovskaya M. L., Malygina E. I. Development of optimal schemes of drug-resistant tuberculosis therapy in experiment. Biology and Experimental Medicine (Biologia i Experimentalnyaya Medicina; In Russian) 2011; 28, 88–93.

39. Yablonskiy P. K., Vinogradova T. I., Levashev Y. N., Pavlova M. V., Zilber E. K., Starshinova A. A., Sapozhnikova N. V., Chernokhaeva I. V., Archakova L. I., Zabolotnykh N. V., Vitovskaya M. L. Preclinical and clinical trials of the new tuberculosis drug perchlozon. Therapeutic Archive (Terapevticheskii Arkhiv; In Russian) 2016; 88, 111–115. doi: 10.17116/terarkh2016883111-115

40. Chernokhaeva I. V., Pavlova M. V., Starshinova A. A., Belyaeva E. N., Sapozhnikova N. V., Gavrilov P. V., Zhuravlev V. Yu., Archakova L. I., Yablonskiy P. K. Efficacy of treatment by perchlozone of multidrug-resistant tuberculosis. Practical Medicine (Praktitscheskaya Medicina; In Russian) 2015; 1, 81–85.

41. Istomina E., Sokolovich E., Pavlova M., Archakova L., Sapozhnikova N., Chernokhaeva I., Yablonskiy P. Clinical example of effective treatment of the recurrence of tuberculosis with multiple dosing stability of mycobacteria. Medicinal Alliance (Medicinskiy Alyans; In Russian) 2019; 7, 57–64.

42. Starshinova A., Belyaeva E., Chernokhaeva I., Sapozhnikova N., Pavlova M., Nazarenko M., Esmedlyaeva D., Diyakova M., Yablonskiy P. Inflammatory response in patients with multiply drug resistant lung tuberculosis against the background of treatment including thioreidoiminomethylpyridinium perchlorate. Medicinal Alliance (Medicinskiy Alyans; In Russian) 2019; 7, 24–31.

43. Pavlova M. V., Ershova E. S., Sapozhnikova N. V., Starshi-nova А. А., Аrchakova L. I., Chernokhaeva I. V. A clinical case of effective treatment of extensive drug resistance tuberculosis with new anti-tuberculosis drugs. Tuberculosis and Lung Diseases (Klinitcheskoe Nablyudeni; In Russian) 2017; 95, 58–62, doi: 10.21292/2075-1230-2017-95-12-58-62

44. Pavlova M. V., Vinogradova T. I., Zabolotnykh N. V., Ershova E. S., Sapozhnikova N. V., Chernokhaeva I. V., Archakova L. I., Vitovskaya M. L., Dogonadze M. Z., Starshinova A. A., Grishko A. N., Yablonsky P. K. Prospects for the use of new generation of anti-tuberculosis drugs in treatment of drug-resistant tuberculosis (experimental and clinical study). Rev. Clin. Pharmacol. Drug Ther. 2018; 16, 33–40. doi: 10.17816/RCF16433-40

45. Potanina O. Hypothyroidism in tuberculosis patients receiving thioureidoiminomethylpyridinium perchlorate therapy. Medicinal Alliance (Medicinskiy Alyans; In Russian) 2018; 6, 41–45.

46. Strygin A. V., Klyausov A. S., Dotsenko A. M., Strygina A. O., Morkovin E. I. Effects of perchlozon and antibodies against human gamma-interferon and CD4 glycoprotein on the immune system of HIV-infected patients with associated pulmonary tuberculosis. Journal of VolgSMU (Vestnik VolgSMU; In Russian) 2017; 62, 42–46. doi: 10.19163/1994-9480-2017-2(62)-42-46

47. Pavlova M., Ershova E., Sapozhnikova N., Chernokhaeva I., Starshinova A., Anisimova A., Yablonskiy P. The first experience of bedaquiline and thioureidoiminomethylpyridinium perchlorate combination in patients with HIV infection. Medicinal Alliance (Medicinskiy Alyans; In Russian) 2019; 7, 22–29.

48. Sosedova L. M., Vokina V. A., Kapustina E. A., Bogomolova E. S. Evaluation of genotoxicity of perchlozone, antituberculous drug. Bull. Exp. Biol. Med. 2020; 169, 48–52. doi: 10.1007/s10517-020-04821-w

49. Churilov L., Korzhikov-Vlakh V., Sinitsyna E., Polyakov D., Darashkevich O., Poida M., Platonova G., Vinogradova T., Utekhin V., Zabolotnykh N., Zinserling V., Yablonsky P., Urtti A., Tennikova T. Enhanced delivery of 4-thioureidoiminomethylpyridinium perchlorate in tuberculosis models with IgG functionalized poly(lactic acid)-based particles. Pharmaceutics 2019; 11, art. no. 2 (20 pp.). doi: 10.3390/pharmaceutics11010002

50. Gopal P., Dick T. The new tuberculosis drug Perchlozone shows cross-resistance with thiacetazone. Int. J. Antimicrob. Agents. 2015; 45, 430–433. doi: 10.1016/j.ijantimicag.2014.12.026