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Synthesis and In vitro Leishmanicidal Activities of Six Quercetin Derivatives
BACKGROUND: Today, leishmaniasis is a widespread, infectious parasitic disease caused by Leishmania spp. Natural-derived compounds are likely to provide a valuable source of new pharmaceuticals, and among them, quercetin derivatives may have antileishmanial effects. The antileishmanial activity of 3...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Medknow Publications & Media Pvt Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5952540/ https://www.ncbi.nlm.nih.gov/pubmed/29862213 http://dx.doi.org/10.4103/abr.abr_76_17 |
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author | Mohajeri, Maryam Saghaei, Lotfollah Ghanadian, Mustafa Saberi, Sedighe Pestechian, Nader Ostadhusseini, Ehsan |
author_facet | Mohajeri, Maryam Saghaei, Lotfollah Ghanadian, Mustafa Saberi, Sedighe Pestechian, Nader Ostadhusseini, Ehsan |
author_sort | Mohajeri, Maryam |
collection | PubMed |
description | BACKGROUND: Today, leishmaniasis is a widespread, infectious parasitic disease caused by Leishmania spp. Natural-derived compounds are likely to provide a valuable source of new pharmaceuticals, and among them, quercetin derivatives may have antileishmanial effects. The antileishmanial activity of 3,5,7,3’,4’-pentahydroxyflavonol (quercetin) derivatives is partly attributed to the position and pKa of phenolic or catechol hydroxyl groups. Therefore, to optimize their leishmanicidal effect, the structural features of quercetin and its derivatives were improved by acylation or alkylation of hydroxyl groups and changing their pKa and consequently their activities. MATERIALS AND METHODS: In this study, during a regioselective method, quercetin derivatives were synthesized. The structures of synthesized compounds were confirmed by mass, IR, (1)H-, and (13)C-NMR spectral data. The antileishmanial activities of compounds 1–6 were compared with glucantime as the standard drug against promastigotes of Leishmania major using standard cell-based leishmanicidal assay. RESULTS: In this study, during a regioselective method, two 7-O-quercetin derivatives (5 and 6), and three quercetin acetate derivatives (2, 3, and 4) were synthesized. In detail, the IC(50) values found against L. major were (1) 2.5 ± 0.92; (2) 2.85 ± 0.99; (3) 15.5 ± 1.95; (4) 13.5 ± 3.5; (5) 2.6 ± 0.57; and (6) 1.3 ± 0.35 μM while IC(50) value of glucantime as the standard drug was 88.5 ± 9.47 μM. CONCLUSIONS: The present study showed an effective antileishmanial activity of quercetin semisynthetic compounds (1–6) against in vitro promastigotes of L. major. Among them, quercetin analogs with more lipophilic and iron-chelating activity showed more antiparasite activity. |
format | Online Article Text |
id | pubmed-5952540 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Medknow Publications & Media Pvt Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-59525402018-06-01 Synthesis and In vitro Leishmanicidal Activities of Six Quercetin Derivatives Mohajeri, Maryam Saghaei, Lotfollah Ghanadian, Mustafa Saberi, Sedighe Pestechian, Nader Ostadhusseini, Ehsan Adv Biomed Res Original Article BACKGROUND: Today, leishmaniasis is a widespread, infectious parasitic disease caused by Leishmania spp. Natural-derived compounds are likely to provide a valuable source of new pharmaceuticals, and among them, quercetin derivatives may have antileishmanial effects. The antileishmanial activity of 3,5,7,3’,4’-pentahydroxyflavonol (quercetin) derivatives is partly attributed to the position and pKa of phenolic or catechol hydroxyl groups. Therefore, to optimize their leishmanicidal effect, the structural features of quercetin and its derivatives were improved by acylation or alkylation of hydroxyl groups and changing their pKa and consequently their activities. MATERIALS AND METHODS: In this study, during a regioselective method, quercetin derivatives were synthesized. The structures of synthesized compounds were confirmed by mass, IR, (1)H-, and (13)C-NMR spectral data. The antileishmanial activities of compounds 1–6 were compared with glucantime as the standard drug against promastigotes of Leishmania major using standard cell-based leishmanicidal assay. RESULTS: In this study, during a regioselective method, two 7-O-quercetin derivatives (5 and 6), and three quercetin acetate derivatives (2, 3, and 4) were synthesized. In detail, the IC(50) values found against L. major were (1) 2.5 ± 0.92; (2) 2.85 ± 0.99; (3) 15.5 ± 1.95; (4) 13.5 ± 3.5; (5) 2.6 ± 0.57; and (6) 1.3 ± 0.35 μM while IC(50) value of glucantime as the standard drug was 88.5 ± 9.47 μM. CONCLUSIONS: The present study showed an effective antileishmanial activity of quercetin semisynthetic compounds (1–6) against in vitro promastigotes of L. major. Among them, quercetin analogs with more lipophilic and iron-chelating activity showed more antiparasite activity. Medknow Publications & Media Pvt Ltd 2018-04-24 /pmc/articles/PMC5952540/ /pubmed/29862213 http://dx.doi.org/10.4103/abr.abr_76_17 Text en Copyright: © 2018 Advanced Biomedical Research http://creativecommons.org/licenses/by-nc-sa/4.0 This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. |
spellingShingle | Original Article Mohajeri, Maryam Saghaei, Lotfollah Ghanadian, Mustafa Saberi, Sedighe Pestechian, Nader Ostadhusseini, Ehsan Synthesis and In vitro Leishmanicidal Activities of Six Quercetin Derivatives |
title | Synthesis and In vitro Leishmanicidal Activities of Six Quercetin Derivatives |
title_full | Synthesis and In vitro Leishmanicidal Activities of Six Quercetin Derivatives |
title_fullStr | Synthesis and In vitro Leishmanicidal Activities of Six Quercetin Derivatives |
title_full_unstemmed | Synthesis and In vitro Leishmanicidal Activities of Six Quercetin Derivatives |
title_short | Synthesis and In vitro Leishmanicidal Activities of Six Quercetin Derivatives |
title_sort | synthesis and in vitro leishmanicidal activities of six quercetin derivatives |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5952540/ https://www.ncbi.nlm.nih.gov/pubmed/29862213 http://dx.doi.org/10.4103/abr.abr_76_17 |
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