Cargando…

The Anti-HIV Actions of 7- and 10-Substituted Camptothecins

Camptothecin (CPT), a traditional anti-tumor drug, has been shown to possess anti-HIV-1 activity. To increase the antiviral potency, the anti-HIV activities of two CPT derivatives, 10-hydroxy-CPT and 7-hydroxymethyl-CPT, were evaluated in vitro. The therapy index (TI) of CPT, 10-hydroxy-CPT and 7-hy...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Yu-Ye, Chen, Shi-Wu, Yang, Liu-Meng, Wang, Rui-Rui, Pang, Wei, Zheng, Yong-Tang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6256925/
https://www.ncbi.nlm.nih.gov/pubmed/20110878
http://dx.doi.org/10.3390/molecules15010138
_version_ 1783374242512896000
author Li, Yu-Ye
Chen, Shi-Wu
Yang, Liu-Meng
Wang, Rui-Rui
Pang, Wei
Zheng, Yong-Tang
author_facet Li, Yu-Ye
Chen, Shi-Wu
Yang, Liu-Meng
Wang, Rui-Rui
Pang, Wei
Zheng, Yong-Tang
author_sort Li, Yu-Ye
collection PubMed
description Camptothecin (CPT), a traditional anti-tumor drug, has been shown to possess anti-HIV-1 activity. To increase the antiviral potency, the anti-HIV activities of two CPT derivatives, 10-hydroxy-CPT and 7-hydroxymethyl-CPT, were evaluated in vitro. The therapy index (TI) of CPT, 10-hydroxy-CPT and 7-hydroxymethyl-CPT against HIV-1(IIIB) in C8166 were 24.2, 4.2 and 198.1, and against clinical isolated strain HIV-1(KM018) in PBMC were 10.3, 3.5 and 66.0, respectively. While the TI of CPT, 10-hydroxy-CPT and 7-hydroxymethyl-CPT against HIV-2(CBL-20) were 34.5, 10.7 and 317.0, respectively, and the TI of the three compounds against HIV-2(ROD) showed the similar values. However, when the antiviral mechanisms were considered, we found there was no inhibition of 7-hydroxymethyl-CPT on viral cell-to-cell transmission, and was no inhibition on reverse transcriptase, protease or integrase in cell-free systems. 7-Hydroxymethyl-CPT showed no selective killing of chronically infected cells after 3 days of incubation. In conclusion, 7-hydroxymethyl-CPT showed more potent anti-HIV activity, while 10-hydroxy-CPT had less efficient activity, compared with the parent CPT. Though the antiviral mechanisms remain to be further elucidated; the modification of -OH residues at C-7 of CPT could enhance the antiviral activity, while of -OH residues at C-10 of CPT had decreased the antiviral activity, which provides the preliminary modification strategy for anti-viral activities enhancement of this compound.
format Online
Article
Text
id pubmed-6256925
institution National Center for Biotechnology Information
language English
publishDate 2009
publisher Molecular Diversity Preservation International
record_format MEDLINE/PubMed
spelling pubmed-62569252018-12-03 The Anti-HIV Actions of 7- and 10-Substituted Camptothecins Li, Yu-Ye Chen, Shi-Wu Yang, Liu-Meng Wang, Rui-Rui Pang, Wei Zheng, Yong-Tang Molecules Article Camptothecin (CPT), a traditional anti-tumor drug, has been shown to possess anti-HIV-1 activity. To increase the antiviral potency, the anti-HIV activities of two CPT derivatives, 10-hydroxy-CPT and 7-hydroxymethyl-CPT, were evaluated in vitro. The therapy index (TI) of CPT, 10-hydroxy-CPT and 7-hydroxymethyl-CPT against HIV-1(IIIB) in C8166 were 24.2, 4.2 and 198.1, and against clinical isolated strain HIV-1(KM018) in PBMC were 10.3, 3.5 and 66.0, respectively. While the TI of CPT, 10-hydroxy-CPT and 7-hydroxymethyl-CPT against HIV-2(CBL-20) were 34.5, 10.7 and 317.0, respectively, and the TI of the three compounds against HIV-2(ROD) showed the similar values. However, when the antiviral mechanisms were considered, we found there was no inhibition of 7-hydroxymethyl-CPT on viral cell-to-cell transmission, and was no inhibition on reverse transcriptase, protease or integrase in cell-free systems. 7-Hydroxymethyl-CPT showed no selective killing of chronically infected cells after 3 days of incubation. In conclusion, 7-hydroxymethyl-CPT showed more potent anti-HIV activity, while 10-hydroxy-CPT had less efficient activity, compared with the parent CPT. Though the antiviral mechanisms remain to be further elucidated; the modification of -OH residues at C-7 of CPT could enhance the antiviral activity, while of -OH residues at C-10 of CPT had decreased the antiviral activity, which provides the preliminary modification strategy for anti-viral activities enhancement of this compound. Molecular Diversity Preservation International 2009-12-31 /pmc/articles/PMC6256925/ /pubmed/20110878 http://dx.doi.org/10.3390/molecules15010138 Text en © 2010 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Li, Yu-Ye
Chen, Shi-Wu
Yang, Liu-Meng
Wang, Rui-Rui
Pang, Wei
Zheng, Yong-Tang
The Anti-HIV Actions of 7- and 10-Substituted Camptothecins
title The Anti-HIV Actions of 7- and 10-Substituted Camptothecins
title_full The Anti-HIV Actions of 7- and 10-Substituted Camptothecins
title_fullStr The Anti-HIV Actions of 7- and 10-Substituted Camptothecins
title_full_unstemmed The Anti-HIV Actions of 7- and 10-Substituted Camptothecins
title_short The Anti-HIV Actions of 7- and 10-Substituted Camptothecins
title_sort anti-hiv actions of 7- and 10-substituted camptothecins
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6256925/
https://www.ncbi.nlm.nih.gov/pubmed/20110878
http://dx.doi.org/10.3390/molecules15010138
work_keys_str_mv AT liyuye theantihivactionsof7and10substitutedcamptothecins
AT chenshiwu theantihivactionsof7and10substitutedcamptothecins
AT yangliumeng theantihivactionsof7and10substitutedcamptothecins
AT wangruirui theantihivactionsof7and10substitutedcamptothecins
AT pangwei theantihivactionsof7and10substitutedcamptothecins
AT zhengyongtang theantihivactionsof7and10substitutedcamptothecins
AT liyuye antihivactionsof7and10substitutedcamptothecins
AT chenshiwu antihivactionsof7and10substitutedcamptothecins
AT yangliumeng antihivactionsof7and10substitutedcamptothecins
AT wangruirui antihivactionsof7and10substitutedcamptothecins
AT pangwei antihivactionsof7and10substitutedcamptothecins
AT zhengyongtang antihivactionsof7and10substitutedcamptothecins