Synthesis of New Indanyl Nucleoside Analogues and their Biological Evaluation on Hepatitis C Virus (HCV) Replicon
Here, we report a convenient synthetic procedure for the preparation of four novel indanyl carbanucleoside derivatives in the racemic form. The action of these compounds against hepatitis C virus was evaluated in vitro using the replicon cell line, Huh7.5 SG. Contrary to our expectations, all these...
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| Language: | English |
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MDPI AG
2019-03-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/24/5/990 |
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| author | Matías E. Gómez Emiliano A. Gentile M. Florencia Martini María L. Cuestas Verónica L. Mathet Graciela Y. Moltrasio Albertina G. Moglioni |
| author_facet | Matías E. Gómez Emiliano A. Gentile M. Florencia Martini María L. Cuestas Verónica L. Mathet Graciela Y. Moltrasio Albertina G. Moglioni |
| author_sort | Matías E. Gómez |
| collection | DOAJ |
| description | Here, we report a convenient synthetic procedure for the preparation of four novel indanyl carbanucleoside derivatives in the racemic form. The action of these compounds against hepatitis C virus was evaluated in vitro using the replicon cell line, Huh7.5 SG. Contrary to our expectations, all these compounds did not inhibit, but rather promoted HCV genotype 1b (HCVg1b) replication. Similar effects have been reported for morphine in the replicon cell lines, Huh7 and Huh8. Several biological experiments and computational studies were performed to elucidate the effect of these compounds on HCVg1b replication. Based on all the experiments performed, we propose that the increase in HCVg1b replication could be mediated, at least in part, by a similar mechanism to that of morphine on the enhancement of this replication. The presence of opioid receptors in Huh7.5 SG cells was indirectly determined for the first time in this work. |
| first_indexed | 2024-12-21T20:03:21Z |
| format | Article |
| id | doaj.art-5d27e515f02642b8a908cb37249da150 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-21T20:03:21Z |
| publishDate | 2019-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-5d27e515f02642b8a908cb37249da1502022-12-21T18:51:55ZengMDPI AGMolecules1420-30492019-03-0124599010.3390/molecules24050990molecules24050990Synthesis of New Indanyl Nucleoside Analogues and their Biological Evaluation on Hepatitis C Virus (HCV) RepliconMatías E. Gómez0Emiliano A. Gentile1M. Florencia Martini2María L. Cuestas3Verónica L. Mathet4Graciela Y. Moltrasio5Albertina G. Moglioni6Cátedra de Química Medicinal, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires C1113AAD, ArgentinaInstituto de Investigaciones en Microbiología y Parasitología Médica, CONICET-Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires C1121ABF, ArgentinaCátedra de Química Medicinal, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires C1113AAD, ArgentinaInstituto de Investigaciones en Microbiología y Parasitología Médica, CONICET-Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires C1121ABF, ArgentinaInstituto de Investigaciones en Microbiología y Parasitología Médica, CONICET-Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires C1121ABF, ArgentinaCátedra de Química Orgánica II, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires C1113AAD, ArgentinaCátedra de Química Medicinal, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires C1113AAD, ArgentinaHere, we report a convenient synthetic procedure for the preparation of four novel indanyl carbanucleoside derivatives in the racemic form. The action of these compounds against hepatitis C virus was evaluated in vitro using the replicon cell line, Huh7.5 SG. Contrary to our expectations, all these compounds did not inhibit, but rather promoted HCV genotype 1b (HCVg1b) replication. Similar effects have been reported for morphine in the replicon cell lines, Huh7 and Huh8. Several biological experiments and computational studies were performed to elucidate the effect of these compounds on HCVg1b replication. Based on all the experiments performed, we propose that the increase in HCVg1b replication could be mediated, at least in part, by a similar mechanism to that of morphine on the enhancement of this replication. The presence of opioid receptors in Huh7.5 SG cells was indirectly determined for the first time in this work.http://www.mdpi.com/1420-3049/24/5/990nucleoside analoguescis-2-amino-1-indanolHCV repliconmolecular modeling |
| spellingShingle | Matías E. Gómez Emiliano A. Gentile M. Florencia Martini María L. Cuestas Verónica L. Mathet Graciela Y. Moltrasio Albertina G. Moglioni Synthesis of New Indanyl Nucleoside Analogues and their Biological Evaluation on Hepatitis C Virus (HCV) Replicon Molecules nucleoside analogues cis-2-amino-1-indanol HCV replicon molecular modeling |
| title | Synthesis of New Indanyl Nucleoside Analogues and their Biological Evaluation on Hepatitis C Virus (HCV) Replicon |
| title_full | Synthesis of New Indanyl Nucleoside Analogues and their Biological Evaluation on Hepatitis C Virus (HCV) Replicon |
| title_fullStr | Synthesis of New Indanyl Nucleoside Analogues and their Biological Evaluation on Hepatitis C Virus (HCV) Replicon |
| title_full_unstemmed | Synthesis of New Indanyl Nucleoside Analogues and their Biological Evaluation on Hepatitis C Virus (HCV) Replicon |
| title_short | Synthesis of New Indanyl Nucleoside Analogues and their Biological Evaluation on Hepatitis C Virus (HCV) Replicon |
| title_sort | synthesis of new indanyl nucleoside analogues and their biological evaluation on hepatitis c virus hcv replicon |
| topic | nucleoside analogues cis-2-amino-1-indanol HCV replicon molecular modeling |
| url | http://www.mdpi.com/1420-3049/24/5/990 |
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