Abstract
Hepatitis B virus (HBV) is the causative agent of B-type hepatitis in humans, a vaccine-preventable disease. Despite the availability of effective vaccines, globally, 2 billion people show evidence of past or current HBV infection, of which 350 million people are persistently infected, with an estimated annual increase of 1 million. There is no cure for chronic HBV infections, which are associated with cirrhotic liver failure and with an increased risk of developing hepatocellular carcinoma. Hepatitis antiviral research has focused primarily on the development of inhibitors of viral polymerase through the use of nucleoside analogues. Therefore, there is an urgent need for the development of non-nucleoside compounds to be used as an alternative or to complement the current therapy. To address this need, 18 isoquinoline alkaloids were evaluated for their potential antiviral activity against HBV in vitro.
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Abbreviations
- HBV:
-
Hepatitis B virus
- CC50 :
-
Concentration resulting in 50 % cytotoxicity
- IC50 :
-
Concentration resulting in 50 % inhibition
- TI:
-
Therapeutic index
References
Neuveut C, Wei Y, Buendia MA (2010) Mechanisms of HBV-related hepatocarcinogenesis. J Hepatol 52:594–604
World Health Organization (2012) Media center hepatitis B fact sheet N°204. http://www.who.int/mediacentre/factsheets/fs204/en/
Agarwal N, Naik S, Aggarwal R, Singh H, Somani SK, Kini D, Pandey R, Choudhuri G, Saraswat VA, Naik SR (2003) Occult hepatitis B virus infection as a cause of cirrhosis of liver in a region with intermediate endemicity. Indian J Gastroenterol 22(4):127–131
Lewis S, Roayaie S, Ward SC, Shyknevsky I, Jibara G, Taouli B (2013) Hepatocellular carcinoma in chronic hepatitis C in the absence of advanced fibrosis or cirrhosis. AJR Am J Roentgenol 200(6):W610–W616. doi:10.2214/AJR.12.9151
Sun P, Yang X, He RQ, Hu QG, Song ZF, Xiong J, Zheng QC (2013) Antiviral therapy after curative treatment of hepatitis B/C virus-related hepatocellular carcinoma: a systematic review of randomized trials. Hepatol Res. doi:10.1111/hepr.12115
Idilman R, Cinar K, Seven G, Bozkus Y, Elhan A, Bozdayi M, Yurdaydin C, Bahar K (2012) Hepatitis B surface antigen seroconversion is associated with favourable long-term clinical outcomes during lamivudine treatment in HBeAg-negative chronic hepatitis B patients. J Viral Hepat 19(3):220–226. doi:10.1111/j.1365-2893.2011.01542.x
Li SY, Qin L, Zhang L, Song XB, Zhou Y, Zhou J, Lu XJ, Cao J, Wang LL, Wang J, Ying BW (2011) Molecular epidemical characteristics of Lamivudine resistance mutations of HBV in southern China. Med Sci Monit 17(10):PH75–PH80
Han Y, Zhang Y, Mei Y, Wang Y, Liu T, Guan Y, Tan D, Liang Y, Yang L, Yi X (2013) Analysis of hepatitis B virus genotyping and drug resistance gene mutations based on massively parallel sequencing. J Virol Methods. doi:10.1016/j.jviromet.2013.06.015
McGonigal KH, Bajjoka IE, Abouljoud MS (2013) Tenofovir-emtricitabine therapy for the prevention of hepatitis B recurrence in four patients after liver transplantation. Pharmacotherapy. doi:10.1002/phar.1306
Billioud G, Pichoud C, Puerstinger G, Neyts J, Zoulim F (2011) The main hepatitis B virus (HBV) mutants resistant to nucleoside analogs are susceptible in vitro to non-nucleoside inhibitors of HBV replication. Antiviral Res 92(2):271–276. doi:10.1016/j.antiviral.2011.08.012 Epub 2011 Aug 18
Sener B (2002) Molecular diversity in the alkaloids of Turkish Fumaria L. species. Acta Pharm Turcica 44:205–212
Sener B (1988) Alkaloids from Turkish corydalis species in “Perspectives in natural products chemistry”. In: Atta-ur-Rahman, LeQuesne PW (eds) Proceedings of the Third International Symposium and Pakistan-U.S. Binational Workshop on Natural Products Chemistry, Karachi, Pakistan. Springer-Verlag, West Germany, pp 569–575
Sells MA, Zelent AZ, Shvartsman M, Acs G (1988) Replicative intermediates of hepatitis B virus in HepG2 cells that produce infectious virions. J Virol 62(8):2836–2844
Doong SL, Tsai CH, Schinazi RF, Liotta DC, Cheng YC (1991) Inhibition of the replication of hepatitis B virus in vitro by 2′,3′-dideoxy-3′-thiacytidine and related analogues. Proc Natl Acad Sci USA 88(19):8495–8499
Jenh AM, Pham PA (2010) Tenofovir disoproxil fumarate in the treatment of chronic hepatitis B. Expert Rev Anti Infect Ther 8(10):1079–1092. doi:10.1586/eri.10.91
Souto AL, Tavares JF, da Silva MS, Diniz MFFM, de Athayde-Filho PF, Filho JMB (2011) Anti-inflammatory activity of alkaloids: an update from 2000 to 2010. Molecules 16:8515–8534. doi:10.3390/molecules16108515
Henriques AT, Limberger RP, Kerber VA, Moreno PRH (2004) Alcalóides: Generalidades Aspectos Básicos. In: Simões CMO, Schenkel EP, Gosmann G, Mello JCP, Mentz LA, Petrovick PR (eds) Farmacognosia: da planta ao medicamento, 5th edn. Editoras of the Universidades Federais de Santa Catarina and Rio Grande do Sul: Porto Alegre/Florianópolis, Brazil, pp 765–792
Aiello A, Fattorusso E, Imperatore C, Irace C, Luciano P, Menna M, Santamaria R, Vitalone R (2011) Zorrimidazolone, a bioactive alkaloid from the non-indigenous Mediterranean stolidobranch Polyandrocarpa zorritensis. Mar Drugs 9:1157–1165
Matthews GV et al (2013) Patterns and causes of suboptimal response to tenofovir based therapy in HIV-HBV infected individuals. Clin Infect Dis 56:e87–e94
Berger J, Hauber J, Hauber R, Geiger T, Cullen BR (1988) Secreted placental alkaline phosphatase: a powerful new quantitative indicator of gene expression in eukaryotic cells. Gene 66:1–10
Cao GW (2009) Clinical relevance and public health significance of hepatitis B virus genomic variations. World J Gastroenterol 15(46):5761–5769
Acknowledgment
The authors would like to thank Dr. Michael K. Lo for critically reading the manuscript. M.A. is supported by National Health and Medical Research Council of Australia (Peter Doherty Biomedical Fellowship #APP1037092). The study is partly funded by The Deanship of Scientific Research, Qassim University, Saudi Arabia, Grant #2106.
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Aljofan, M., Netter, H.J., Aljarbou, A.N. et al. Anti-hepatitis B activity of isoquinoline alkaloids of plant origin. Arch Virol 159, 1119–1128 (2014). https://doi.org/10.1007/s00705-013-1937-7
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DOI: https://doi.org/10.1007/s00705-013-1937-7