Antiviral activity against the hepatitis C virus (HCV) of 1-indanone thiosemicarbazones and their inclusion complexes with hydroxypropyl-β-cyclodextrin - PubMed (original) (raw)
. 2012 Oct 9;47(3):596-603.
doi: 10.1016/j.ejps.2012.07.018. Epub 2012 Aug 3.
Affiliations
- PMID: 22885176
- DOI: 10.1016/j.ejps.2012.07.018
Antiviral activity against the hepatitis C virus (HCV) of 1-indanone thiosemicarbazones and their inclusion complexes with hydroxypropyl-β-cyclodextrin
Romina J Glisoni et al. Eur J Pharm Sci. 2012.
Abstract
The hepatitis C virus (HCV) is a major cause of acute and chronic hepatitis in humans. Approximately 5% of the infected people die from cirrhosis or hepatocellular carcinoma. The current standard therapy comprises a combination of pegylated-interferon alpha and ribavirin. Due to the relatively low effectiveness, the prohibitive costs and the extensive side effects of the treatment, an intense research for new direct-acting anti-HCV agents is taking place. Furthermore, NS3 protease inhibitors recently introduced into the market are not effective against all HCV subgenotypes. Thiosemicarbazones (TSCs) have shown antiviral activity against a wide range of DNA and RNA viruses. However, their extremely low aqueous solubility and high self-aggregation tendency often preclude their reliable biological evaluation in vitro. In this work, we investigated and compared for the first time the anti-HCV activity of two 1-indanone TSCs, namely 5,6-dimethoxy-1-indanone TSC and 5,6-dimethoxy-1-indanone N4-allyl TSC, and their inclusion complexes with hydroxypropyl-β-cyclodextrin (HPβ-CD) in Huh-7.5 cells containing the full-length and the subgenomic subgenotype 1b HCV replicon system. Studies of physical stability in culture medium showed that free TSCs precipitated rapidly and formed submicron aggregates. Conversely, TSC complexation with HPβ-CD led to more stable systems with minimal size growth and drug concentration loss. More importantly, both TSCs and their inclusion complexes displayed a potent suppression of the HCV replication in both cell lines with no cytotoxic effects. The mechanism likely involves the inhibition of non-structural proteins of the virus. In addition, findings suggested that the cyclodextrin released the drug to the culture medium over time. This platform could be exploited for the study of the drug toxicity and pharmacokinetics animal models.
Copyright © 2012 Elsevier B.V. All rights reserved.
Similar articles
- Complexation of a 1-Indanone Thiosemicarbazone with Hydroxypropyl-β-Cyclodextrin Enhances Its Activity Against a Hepatitis C Virus Surrogate Model.
Glisoni RJ, Castro EF, Cavallaro LV, Moglioni AG, Sosnik A. Glisoni RJ, et al. J Nanosci Nanotechnol. 2015 Jun;15(6):4224-8. doi: 10.1166/jnn.2015.9613. J Nanosci Nanotechnol. 2015. PMID: 26369033 - Enhancement of antiviral activity against hepatitis C virus in vitro by interferon combination therapy.
Okuse C, Rinaudo JA, Farrar K, Wells F, Korba BE. Okuse C, et al. Antiviral Res. 2005 Jan;65(1):23-34. doi: 10.1016/j.antiviral.2004.09.002. Antiviral Res. 2005. PMID: 15652968 - The non-immunosuppressive cyclosporin DEBIO-025 is a potent inhibitor of hepatitis C virus replication in vitro.
Paeshuyse J, Kaul A, De Clercq E, Rosenwirth B, Dumont JM, Scalfaro P, Bartenschlager R, Neyts J. Paeshuyse J, et al. Hepatology. 2006 Apr;43(4):761-70. doi: 10.1002/hep.21102. Hepatology. 2006. PMID: 16557546 - Selective inhibitors of hepatitis C virus replication.
Neyts J. Neyts J. Antiviral Res. 2006 Sep;71(2-3):363-71. doi: 10.1016/j.antiviral.2006.06.006. Epub 2006 Jun 23. Antiviral Res. 2006. PMID: 16843538 Review. - Hepatitis C virus resistance to protease inhibitors.
Halfon P, Locarnini S. Halfon P, et al. J Hepatol. 2011 Jul;55(1):192-206. doi: 10.1016/j.jhep.2011.01.011. Epub 2011 Feb 1. J Hepatol. 2011. PMID: 21284949 Review.
Cited by
- New Mononuclear and Binuclear Cu(II), Co(II), Ni(II), and Zn(II) Thiosemicarbazone Complexes with Potential Biological Activity: Antimicrobial and Molecular Docking Study.
Gaber A, Refat MS, Belal AAM, El-Deen IM, Hassan N, Zakaria R, Alhomrani M, Alamri AS, Alsanie WF, M Saied E. Gaber A, et al. Molecules. 2021 Apr 15;26(8):2288. doi: 10.3390/molecules26082288. Molecules. 2021. PMID: 33920893 Free PMC article. - Cyclodextrins in the antiviral therapy.
Jicsinszky L, Martina K, Cravotto G. Jicsinszky L, et al. J Drug Deliv Sci Technol. 2021 Aug;64:102589. doi: 10.1016/j.jddst.2021.102589. Epub 2021 May 20. J Drug Deliv Sci Technol. 2021. PMID: 34035845 Free PMC article. Review. - Synthesis, Crystal Structure, and Biological Activity of a Multidentate Calix[4]arene Ligand Doubly Functionalized by 2-Hydroxybenzeledene-Thiosemicarbazone.
Bahojb Noruzi E, Shaabani B, Geremia S, Hickey N, Nitti P, Kafil HS. Bahojb Noruzi E, et al. Molecules. 2020 Jan 16;25(2):370. doi: 10.3390/molecules25020370. Molecules. 2020. PMID: 31963211 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources