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Synthesis and biological evaluation against Leishmania donovani of novel hybrid molecules containing indazole-based 2-pyrone scaffolds
A series of novel indazole-pyrone hybrids were synthesized by a one pot reaction between -alkyl-6(5)-nitroindazoles and 2-pyrone (4-hydroxy-6-methyl-2 -pyran-2-one) using indium or stannous chloride as the reducing system in the presence of acetic acid in tetrahydrofuran. The hybrid molecules were o...
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| Published in: | MedChemComm 2019-01, Vol.10 (1), p.120-127 |
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| creator | El Ghozlani, M Bouissane, L Berkani, M Mojahidi, S Allam, A Menendez, C Cojean, S Loiseau, P M Baltas, M Rakib, E M |
| description | A series of novel indazole-pyrone hybrids were synthesized by a one pot reaction between
-alkyl-6(5)-nitroindazoles and 2-pyrone (4-hydroxy-6-methyl-2
-pyran-2-one) using indium or stannous chloride as the reducing system in the presence of acetic acid in tetrahydrofuran. The hybrid molecules were obtained in good to excellent yields (72-92%) and characterized by NMR and single crystal X-ray diffraction. Nineteen compounds were tested
against both
(MHOM/ET/67/HU3, also called LV9) axenic and intramacrophage amastigotes. Among all, five compounds showed anti-leishmanial activity against intracellular
with an IC
in the range of 2.25 to 62.56 μM. 3-(1-(3-Chloro-2-ethyl-2
-indazol-6-ylamino)ethylidene)-6-methyl-3
-pyran-2,4-dione
was found to be the most active compound for axenic amastigotes and intramacrophage amastigotes of
with IC
values of 2.48 ± 1.02 μM and 2.25 ± 1.89 μM, respectively. However, the cytotoxicity of the most promising compound justifies further pharmacomodulations. |
| doi_str_mv | 10.1039/C8MD00475G |
| format | article |
| fullrecord | <record><control><sourceid>proquest_hal_p</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_hal_02059320v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2183184969</sourcerecordid><originalsourceid>FETCH-LOGICAL-c385t-1f098822e47c5e7b538353c23e563be3a1948067a7dfbbce81fc180f32e93c683</originalsourceid><addsrcrecordid>eNpdkcFu1DAQhi0EolXphQdAlrhApcDYEyfOsdpCi7SIA3COHGey68qxlzhZaXkAnhtX2y4Sc5lfM9-MZvQz9lrABwHYfFzprzcAZa1un7FzCSUUUgnx_KQBz9hlSveQA6XWTfmSnSHUdakrOGd_vh_CvKXkEjeh552LPm6cNZ7T3vjFzC4GbjbGhTTzNbm0HU1whvcxxH1WPA48K_J8e-gm1_MxerKLp8RtDHOec2HDXejN79woOpOo57LYHaYYiCdrhiH6Pr1iLwbjE10-5gv28_OnH6u7Yv3t9svqel1Y1GouxACN1lJSWVtFdadQo0IrkVSFHaERTamhqk3dD11nSYvBCg0DSmrQVhov2Pvj3q3x7W5yo5kObTSuvbtetw81kKAalLAXmX13ZHdT_LVQmtvRJUvem0BxSa0UGoUum6rJ6Nv_0Pu4TCF_kqkaFEjUkKmrI2WnmNJEw-kCAe2Dme0_MzP85nHl0o3Un9An6_AvdWeZrQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2170502380</pqid></control><display><type>article</type><title>Synthesis and biological evaluation against Leishmania donovani of novel hybrid molecules containing indazole-based 2-pyrone scaffolds</title><source>PubMed Central</source><source>Royal Society of Chemistry:Jisc Collections:Royal Society of Chemistry Read and Publish 2022-2024 (reading list)</source><creator>El Ghozlani, M ; Bouissane, L ; Berkani, M ; Mojahidi, S ; Allam, A ; Menendez, C ; Cojean, S ; Loiseau, P M ; Baltas, M ; Rakib, E M</creator><creatorcontrib>El Ghozlani, M ; Bouissane, L ; Berkani, M ; Mojahidi, S ; Allam, A ; Menendez, C ; Cojean, S ; Loiseau, P M ; Baltas, M ; Rakib, E M</creatorcontrib><description>A series of novel indazole-pyrone hybrids were synthesized by a one pot reaction between
-alkyl-6(5)-nitroindazoles and 2-pyrone (4-hydroxy-6-methyl-2
-pyran-2-one) using indium or stannous chloride as the reducing system in the presence of acetic acid in tetrahydrofuran. The hybrid molecules were obtained in good to excellent yields (72-92%) and characterized by NMR and single crystal X-ray diffraction. Nineteen compounds were tested
against both
(MHOM/ET/67/HU3, also called LV9) axenic and intramacrophage amastigotes. Among all, five compounds showed anti-leishmanial activity against intracellular
with an IC
in the range of 2.25 to 62.56 μM. 3-(1-(3-Chloro-2-ethyl-2
-indazol-6-ylamino)ethylidene)-6-methyl-3
-pyran-2,4-dione
was found to be the most active compound for axenic amastigotes and intramacrophage amastigotes of
with IC
values of 2.48 ± 1.02 μM and 2.25 ± 1.89 μM, respectively. However, the cytotoxicity of the most promising compound justifies further pharmacomodulations.</description><identifier>ISSN: 2040-2503</identifier><identifier>ISSN: 2040-2511</identifier><identifier>EISSN: 2040-2511</identifier><identifier>DOI: 10.1039/C8MD00475G</identifier><identifier>PMID: 30774860</identifier><language>eng</language><publisher>England: Royal Society of Chemistry</publisher><subject>Acetic acid ; Amastigotes ; Chemical Sciences ; Chemical synthesis ; Cytotoxicity ; Diketones ; Hybrids ; Indium ; Leishmania donovani ; NMR ; Nuclear magnetic resonance ; Pharmacology ; Single crystals ; Stannous chloride ; Tetrahydrofuran ; Toxicity ; X-ray diffraction</subject><ispartof>MedChemComm, 2019-01, Vol.10 (1), p.120-127</ispartof><rights>Copyright Royal Society of Chemistry 2019</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c385t-1f098822e47c5e7b538353c23e563be3a1948067a7dfbbce81fc180f32e93c683</citedby><cites>FETCH-LOGICAL-c385t-1f098822e47c5e7b538353c23e563be3a1948067a7dfbbce81fc180f32e93c683</cites><orcidid>0000-0002-2121-4708 ; 0000-0002-2231-1956 ; 0000-0002-8785-7095</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,786,790,891,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30774860$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-02059320$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>El Ghozlani, M</creatorcontrib><creatorcontrib>Bouissane, L</creatorcontrib><creatorcontrib>Berkani, M</creatorcontrib><creatorcontrib>Mojahidi, S</creatorcontrib><creatorcontrib>Allam, A</creatorcontrib><creatorcontrib>Menendez, C</creatorcontrib><creatorcontrib>Cojean, S</creatorcontrib><creatorcontrib>Loiseau, P M</creatorcontrib><creatorcontrib>Baltas, M</creatorcontrib><creatorcontrib>Rakib, E M</creatorcontrib><title>Synthesis and biological evaluation against Leishmania donovani of novel hybrid molecules containing indazole-based 2-pyrone scaffolds</title><title>MedChemComm</title><addtitle>Medchemcomm</addtitle><description>A series of novel indazole-pyrone hybrids were synthesized by a one pot reaction between
-alkyl-6(5)-nitroindazoles and 2-pyrone (4-hydroxy-6-methyl-2
-pyran-2-one) using indium or stannous chloride as the reducing system in the presence of acetic acid in tetrahydrofuran. The hybrid molecules were obtained in good to excellent yields (72-92%) and characterized by NMR and single crystal X-ray diffraction. Nineteen compounds were tested
against both
(MHOM/ET/67/HU3, also called LV9) axenic and intramacrophage amastigotes. Among all, five compounds showed anti-leishmanial activity against intracellular
with an IC
in the range of 2.25 to 62.56 μM. 3-(1-(3-Chloro-2-ethyl-2
-indazol-6-ylamino)ethylidene)-6-methyl-3
-pyran-2,4-dione
was found to be the most active compound for axenic amastigotes and intramacrophage amastigotes of
with IC
values of 2.48 ± 1.02 μM and 2.25 ± 1.89 μM, respectively. However, the cytotoxicity of the most promising compound justifies further pharmacomodulations.</description><subject>Acetic acid</subject><subject>Amastigotes</subject><subject>Chemical Sciences</subject><subject>Chemical synthesis</subject><subject>Cytotoxicity</subject><subject>Diketones</subject><subject>Hybrids</subject><subject>Indium</subject><subject>Leishmania donovani</subject><subject>NMR</subject><subject>Nuclear magnetic resonance</subject><subject>Pharmacology</subject><subject>Single crystals</subject><subject>Stannous chloride</subject><subject>Tetrahydrofuran</subject><subject>Toxicity</subject><subject>X-ray diffraction</subject><issn>2040-2503</issn><issn>2040-2511</issn><issn>2040-2511</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNpdkcFu1DAQhi0EolXphQdAlrhApcDYEyfOsdpCi7SIA3COHGey68qxlzhZaXkAnhtX2y4Sc5lfM9-MZvQz9lrABwHYfFzprzcAZa1un7FzCSUUUgnx_KQBz9hlSveQA6XWTfmSnSHUdakrOGd_vh_CvKXkEjeh552LPm6cNZ7T3vjFzC4GbjbGhTTzNbm0HU1whvcxxH1WPA48K_J8e-gm1_MxerKLp8RtDHOec2HDXejN79woOpOo57LYHaYYiCdrhiH6Pr1iLwbjE10-5gv28_OnH6u7Yv3t9svqel1Y1GouxACN1lJSWVtFdadQo0IrkVSFHaERTamhqk3dD11nSYvBCg0DSmrQVhov2Pvj3q3x7W5yo5kObTSuvbtetw81kKAalLAXmX13ZHdT_LVQmtvRJUvem0BxSa0UGoUum6rJ6Nv_0Pu4TCF_kqkaFEjUkKmrI2WnmNJEw-kCAe2Dme0_MzP85nHl0o3Un9An6_AvdWeZrQ</recordid><startdate>20190101</startdate><enddate>20190101</enddate><creator>El Ghozlani, M</creator><creator>Bouissane, L</creator><creator>Berkani, M</creator><creator>Mojahidi, S</creator><creator>Allam, A</creator><creator>Menendez, C</creator><creator>Cojean, S</creator><creator>Loiseau, P M</creator><creator>Baltas, M</creator><creator>Rakib, E M</creator><general>Royal Society of Chemistry</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QO</scope><scope>7T5</scope><scope>7T7</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><orcidid>https://orcid.org/0000-0002-2121-4708</orcidid><orcidid>https://orcid.org/0000-0002-2231-1956</orcidid><orcidid>https://orcid.org/0000-0002-8785-7095</orcidid></search><sort><creationdate>20190101</creationdate><title>Synthesis and biological evaluation against Leishmania donovani of novel hybrid molecules containing indazole-based 2-pyrone scaffolds</title><author>El Ghozlani, M ; Bouissane, L ; Berkani, M ; Mojahidi, S ; Allam, A ; Menendez, C ; Cojean, S ; Loiseau, P M ; Baltas, M ; Rakib, E M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c385t-1f098822e47c5e7b538353c23e563be3a1948067a7dfbbce81fc180f32e93c683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Acetic acid</topic><topic>Amastigotes</topic><topic>Chemical Sciences</topic><topic>Chemical synthesis</topic><topic>Cytotoxicity</topic><topic>Diketones</topic><topic>Hybrids</topic><topic>Indium</topic><topic>Leishmania donovani</topic><topic>NMR</topic><topic>Nuclear magnetic resonance</topic><topic>Pharmacology</topic><topic>Single crystals</topic><topic>Stannous chloride</topic><topic>Tetrahydrofuran</topic><topic>Toxicity</topic><topic>X-ray diffraction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>El Ghozlani, M</creatorcontrib><creatorcontrib>Bouissane, L</creatorcontrib><creatorcontrib>Berkani, M</creatorcontrib><creatorcontrib>Mojahidi, S</creatorcontrib><creatorcontrib>Allam, A</creatorcontrib><creatorcontrib>Menendez, C</creatorcontrib><creatorcontrib>Cojean, S</creatorcontrib><creatorcontrib>Loiseau, P M</creatorcontrib><creatorcontrib>Baltas, M</creatorcontrib><creatorcontrib>Rakib, E M</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><jtitle>MedChemComm</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>El Ghozlani, M</au><au>Bouissane, L</au><au>Berkani, M</au><au>Mojahidi, S</au><au>Allam, A</au><au>Menendez, C</au><au>Cojean, S</au><au>Loiseau, P M</au><au>Baltas, M</au><au>Rakib, E M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis and biological evaluation against Leishmania donovani of novel hybrid molecules containing indazole-based 2-pyrone scaffolds</atitle><jtitle>MedChemComm</jtitle><addtitle>Medchemcomm</addtitle><date>2019-01-01</date><risdate>2019</risdate><volume>10</volume><issue>1</issue><spage>120</spage><epage>127</epage><pages>120-127</pages><issn>2040-2503</issn><issn>2040-2511</issn><eissn>2040-2511</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>A series of novel indazole-pyrone hybrids were synthesized by a one pot reaction between
-alkyl-6(5)-nitroindazoles and 2-pyrone (4-hydroxy-6-methyl-2
-pyran-2-one) using indium or stannous chloride as the reducing system in the presence of acetic acid in tetrahydrofuran. The hybrid molecules were obtained in good to excellent yields (72-92%) and characterized by NMR and single crystal X-ray diffraction. Nineteen compounds were tested
against both
(MHOM/ET/67/HU3, also called LV9) axenic and intramacrophage amastigotes. Among all, five compounds showed anti-leishmanial activity against intracellular
with an IC
in the range of 2.25 to 62.56 μM. 3-(1-(3-Chloro-2-ethyl-2
-indazol-6-ylamino)ethylidene)-6-methyl-3
-pyran-2,4-dione
was found to be the most active compound for axenic amastigotes and intramacrophage amastigotes of
with IC
values of 2.48 ± 1.02 μM and 2.25 ± 1.89 μM, respectively. However, the cytotoxicity of the most promising compound justifies further pharmacomodulations.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>30774860</pmid><doi>10.1039/C8MD00475G</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-2121-4708</orcidid><orcidid>https://orcid.org/0000-0002-2231-1956</orcidid><orcidid>https://orcid.org/0000-0002-8785-7095</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | MedChemComm, 2019-01, Vol.10 (1), p.120-127 |
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| source | PubMed Central; Royal Society of Chemistry:Jisc Collections:Royal Society of Chemistry Read and Publish 2022-2024 (reading list) |
| subjects | Acetic acid Amastigotes Chemical Sciences Chemical synthesis Cytotoxicity Diketones Hybrids Indium Leishmania donovani NMR Nuclear magnetic resonance Pharmacology Single crystals Stannous chloride Tetrahydrofuran Toxicity X-ray diffraction |
| title | Synthesis and biological evaluation against Leishmania donovani of novel hybrid molecules containing indazole-based 2-pyrone scaffolds |
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