Synthesis and antifungal activity of new hybrids pyrimido[4,5-d]pyridazinone-N-acylhydrazones
[Display omitted] •Pyrimido[4,5-d]pyridazinone-N-acylhydrazones were synthesized by simple methodologies.•Antifungal activity of compounds was evaluated against P.brasiliensis and Candida spp.•Six compounds showed inhibition against Pb18 with MIC of 0.125 to 64 µg.mL−1.•N-acylhydrazone 5a showed pot...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2020-07, Vol.30 (14), p.127244-127244, Article 127244 |
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| creator | Rozada, Andrew M.F. Rodrigues-Vendramini, Franciele A.V. Gonçalves, Davana S. Rosa, Fernanda A. Basso, Ernani A. Seixas, Flávio A.V. Kioshima, Érika S. Gauze, Gisele F. |
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•Pyrimido[4,5-d]pyridazinone-N-acylhydrazones were synthesized by simple methodologies.•Antifungal activity of compounds was evaluated against P.brasiliensis and Candida spp.•Six compounds showed inhibition against Pb18 with MIC of 0.125 to 64 µg.mL−1.•N-acylhydrazone 5a showed potent fungicidal profile with MFC of 0.5 µg mL−1.•Compound 5a showed good synergic effect with amphotericin B and not showed toxicity.
Paracoccidioidomycosis is an endemic mycosis in Latin America for which there is a high mortality rate and limited treatment options. There are no specific drugs to treat the systemic disease. Thus, there is a need for further studies focused on the development of specific drugs. In this work we synthesized new hybrids pyrimido[4,5-d]pyridazinone-N-acylhydrazone (5a-p) by simple methodologies with good yields. The antifungal activity of compounds was evaluated against P. brasiliensis (Pb18) and Candida spp. Compounds 5a, 5f, 5i, 5 k, 5m and 5n showed significant inhibition against Pb18 with MIC of 0.125 to 64 µg mL−1. Compound 5a is the most promising, showing potent fungicidal profile with MFC of 0.5 µg mL−1, synergic effect with amphotericin B, besides showing no toxicity against HeLa and Vero cells. |
| doi_str_mv | 10.1016/j.bmcl.2020.127244 |
| format | Article |
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•Pyrimido[4,5-d]pyridazinone-N-acylhydrazones were synthesized by simple methodologies.•Antifungal activity of compounds was evaluated against P.brasiliensis and Candida spp.•Six compounds showed inhibition against Pb18 with MIC of 0.125 to 64 µg.mL−1.•N-acylhydrazone 5a showed potent fungicidal profile with MFC of 0.5 µg mL−1.•Compound 5a showed good synergic effect with amphotericin B and not showed toxicity.
Paracoccidioidomycosis is an endemic mycosis in Latin America for which there is a high mortality rate and limited treatment options. There are no specific drugs to treat the systemic disease. Thus, there is a need for further studies focused on the development of specific drugs. In this work we synthesized new hybrids pyrimido[4,5-d]pyridazinone-N-acylhydrazone (5a-p) by simple methodologies with good yields. The antifungal activity of compounds was evaluated against P. brasiliensis (Pb18) and Candida spp. Compounds 5a, 5f, 5i, 5 k, 5m and 5n showed significant inhibition against Pb18 with MIC of 0.125 to 64 µg mL−1. Compound 5a is the most promising, showing potent fungicidal profile with MFC of 0.5 µg mL−1, synergic effect with amphotericin B, besides showing no toxicity against HeLa and Vero cells.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2020.127244</identifier><language>eng</language><publisher>Elsevier Ltd</publisher><subject>Antifungal ; Fungicidal ; N-acylhydrazones ; Neglected disease ; Paracoccidioidomycosis</subject><ispartof>Bioorganic & medicinal chemistry letters, 2020-07, Vol.30 (14), p.127244-127244, Article 127244</ispartof><rights>2020 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c333t-bca64819cf82efb37390198a3c0f51eb66a192a0c8c6746b8f378812525699c13</citedby><cites>FETCH-LOGICAL-c333t-bca64819cf82efb37390198a3c0f51eb66a192a0c8c6746b8f378812525699c13</cites><orcidid>0000-0003-0027-7117</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0960894X20303498$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids></links><search><creatorcontrib>Rozada, Andrew M.F.</creatorcontrib><creatorcontrib>Rodrigues-Vendramini, Franciele A.V.</creatorcontrib><creatorcontrib>Gonçalves, Davana S.</creatorcontrib><creatorcontrib>Rosa, Fernanda A.</creatorcontrib><creatorcontrib>Basso, Ernani A.</creatorcontrib><creatorcontrib>Seixas, Flávio A.V.</creatorcontrib><creatorcontrib>Kioshima, Érika S.</creatorcontrib><creatorcontrib>Gauze, Gisele F.</creatorcontrib><title>Synthesis and antifungal activity of new hybrids pyrimido[4,5-d]pyridazinone-N-acylhydrazones</title><title>Bioorganic & medicinal chemistry letters</title><description>[Display omitted]
•Pyrimido[4,5-d]pyridazinone-N-acylhydrazones were synthesized by simple methodologies.•Antifungal activity of compounds was evaluated against P.brasiliensis and Candida spp.•Six compounds showed inhibition against Pb18 with MIC of 0.125 to 64 µg.mL−1.•N-acylhydrazone 5a showed potent fungicidal profile with MFC of 0.5 µg mL−1.•Compound 5a showed good synergic effect with amphotericin B and not showed toxicity.
Paracoccidioidomycosis is an endemic mycosis in Latin America for which there is a high mortality rate and limited treatment options. There are no specific drugs to treat the systemic disease. Thus, there is a need for further studies focused on the development of specific drugs. In this work we synthesized new hybrids pyrimido[4,5-d]pyridazinone-N-acylhydrazone (5a-p) by simple methodologies with good yields. The antifungal activity of compounds was evaluated against P. brasiliensis (Pb18) and Candida spp. Compounds 5a, 5f, 5i, 5 k, 5m and 5n showed significant inhibition against Pb18 with MIC of 0.125 to 64 µg mL−1. Compound 5a is the most promising, showing potent fungicidal profile with MFC of 0.5 µg mL−1, synergic effect with amphotericin B, besides showing no toxicity against HeLa and Vero cells.</description><subject>Antifungal</subject><subject>Fungicidal</subject><subject>N-acylhydrazones</subject><subject>Neglected disease</subject><subject>Paracoccidioidomycosis</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kEtLxDAUhYMoOI7-AVddurBjXk0TcCPiCwZdqCDIENI8nAyddEw6I51fb0tdu7hczuWcC-cD4BzBGYKIXa1m1VrXMwxxf8AlpvQATBBlNCcUFodgAgWDORf04xicpLSCEFFI6QQsXrvQLm3yKVPB9NN6tw1fqs6Ubv3Ot13WuCzYn2zZVdGblG266NfeNJ_0ssjNYpBG7X1ogs2fc6W7etmZqPa9TqfgyKk62bO_PQXv93dvt4_5_OXh6fZmnmtCSJtXWjHKkdCOY-sqUhIBkeCKaOgKZCvGFBJYQc01KymruCMl5wgXuGBCaESm4GL8u4nN99amVq590rauVbDNNklMERaigIL2VjxadWxSitbJTd9HxU4iKAeWciUHlnJgKUeWfeh6DNm-xM7bKJP2NmhrfLS6labx_8V_ATzAfcQ</recordid><startdate>20200715</startdate><enddate>20200715</enddate><creator>Rozada, Andrew M.F.</creator><creator>Rodrigues-Vendramini, Franciele A.V.</creator><creator>Gonçalves, Davana S.</creator><creator>Rosa, Fernanda A.</creator><creator>Basso, Ernani A.</creator><creator>Seixas, Flávio A.V.</creator><creator>Kioshima, Érika S.</creator><creator>Gauze, Gisele F.</creator><general>Elsevier Ltd</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-0027-7117</orcidid></search><sort><creationdate>20200715</creationdate><title>Synthesis and antifungal activity of new hybrids pyrimido[4,5-d]pyridazinone-N-acylhydrazones</title><author>Rozada, Andrew M.F. ; Rodrigues-Vendramini, Franciele A.V. ; Gonçalves, Davana S. ; Rosa, Fernanda A. ; Basso, Ernani A. ; Seixas, Flávio A.V. ; Kioshima, Érika S. ; Gauze, Gisele F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c333t-bca64819cf82efb37390198a3c0f51eb66a192a0c8c6746b8f378812525699c13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Antifungal</topic><topic>Fungicidal</topic><topic>N-acylhydrazones</topic><topic>Neglected disease</topic><topic>Paracoccidioidomycosis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rozada, Andrew M.F.</creatorcontrib><creatorcontrib>Rodrigues-Vendramini, Franciele A.V.</creatorcontrib><creatorcontrib>Gonçalves, Davana S.</creatorcontrib><creatorcontrib>Rosa, Fernanda A.</creatorcontrib><creatorcontrib>Basso, Ernani A.</creatorcontrib><creatorcontrib>Seixas, Flávio A.V.</creatorcontrib><creatorcontrib>Kioshima, Érika S.</creatorcontrib><creatorcontrib>Gauze, Gisele F.</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rozada, Andrew M.F.</au><au>Rodrigues-Vendramini, Franciele A.V.</au><au>Gonçalves, Davana S.</au><au>Rosa, Fernanda A.</au><au>Basso, Ernani A.</au><au>Seixas, Flávio A.V.</au><au>Kioshima, Érika S.</au><au>Gauze, Gisele F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis and antifungal activity of new hybrids pyrimido[4,5-d]pyridazinone-N-acylhydrazones</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><date>2020-07-15</date><risdate>2020</risdate><volume>30</volume><issue>14</issue><spage>127244</spage><epage>127244</epage><pages>127244-127244</pages><artnum>127244</artnum><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>[Display omitted]
•Pyrimido[4,5-d]pyridazinone-N-acylhydrazones were synthesized by simple methodologies.•Antifungal activity of compounds was evaluated against P.brasiliensis and Candida spp.•Six compounds showed inhibition against Pb18 with MIC of 0.125 to 64 µg.mL−1.•N-acylhydrazone 5a showed potent fungicidal profile with MFC of 0.5 µg mL−1.•Compound 5a showed good synergic effect with amphotericin B and not showed toxicity.
Paracoccidioidomycosis is an endemic mycosis in Latin America for which there is a high mortality rate and limited treatment options. There are no specific drugs to treat the systemic disease. Thus, there is a need for further studies focused on the development of specific drugs. In this work we synthesized new hybrids pyrimido[4,5-d]pyridazinone-N-acylhydrazone (5a-p) by simple methodologies with good yields. The antifungal activity of compounds was evaluated against P. brasiliensis (Pb18) and Candida spp. Compounds 5a, 5f, 5i, 5 k, 5m and 5n showed significant inhibition against Pb18 with MIC of 0.125 to 64 µg mL−1. Compound 5a is the most promising, showing potent fungicidal profile with MFC of 0.5 µg mL−1, synergic effect with amphotericin B, besides showing no toxicity against HeLa and Vero cells.</abstract><pub>Elsevier Ltd</pub><doi>10.1016/j.bmcl.2020.127244</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0003-0027-7117</orcidid></addata></record> |
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| subjects | Antifungal Fungicidal N-acylhydrazones Neglected disease Paracoccidioidomycosis |
| title | Synthesis and antifungal activity of new hybrids pyrimido[4,5-d]pyridazinone-N-acylhydrazones |
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