Synthesis and in vitro evaluation of hydrazinyl phthalazines against malaria parasite, Plasmodium falciparum
[Display omitted] In this report, we describe the synthesis of 1-(Phthalazin-4-yl)-hydrazine using bronsted acidic ionic liquids and demonstrate their ability to inhibit asexual stage development of human malaria parasite, Plasmodium falciparum. Through computational studies, we short-listed chemica...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2016-07, Vol.26 (14), p.3300-3306 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | Subramanian, Gowtham Babu Rajeev, C.P. Mohan, Chakrabhavi Dhananjaya Sinha, Ameya Chu, Trang T.T. Anusha, Sebastian Ximei, Huang Fuchs, Julian E. Bender, Andreas Rangappa, Kanchugarakoppal S. Chandramohanadas, Rajesh Basappa |
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In this report, we describe the synthesis of 1-(Phthalazin-4-yl)-hydrazine using bronsted acidic ionic liquids and demonstrate their ability to inhibit asexual stage development of human malaria parasite, Plasmodium falciparum. Through computational studies, we short-listed chemical scaffolds with potential binding affinity to an essential parasite protein, dihydroorotate dehydrogenase (DHODH). Further, these compounds were synthesized in the lab and tested against P. falciparum. Several compounds from our library showed inhibitory activity at low micro-molar concentrations with minimal cytotoxic effects. These results indicate the potential of hydralazine derivatives as reference scaffolds to develop novel antimalarials. |
| doi_str_mv | 10.1016/j.bmcl.2016.05.049 |
| format | Article |
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In this report, we describe the synthesis of 1-(Phthalazin-4-yl)-hydrazine using bronsted acidic ionic liquids and demonstrate their ability to inhibit asexual stage development of human malaria parasite, Plasmodium falciparum. Through computational studies, we short-listed chemical scaffolds with potential binding affinity to an essential parasite protein, dihydroorotate dehydrogenase (DHODH). Further, these compounds were synthesized in the lab and tested against P. falciparum. Several compounds from our library showed inhibitory activity at low micro-molar concentrations with minimal cytotoxic effects. These results indicate the potential of hydralazine derivatives as reference scaffolds to develop novel antimalarials.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2016.05.049</identifier><identifier>PMID: 27261180</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; Antimalarials ; Antimalarials - chemical synthesis ; Antimalarials - chemistry ; Antimalarials - pharmacology ; Bronsted acidic ionic liquids ; Cell Line ; Dihydroorotate dehydrogenase ; Dogs ; Dose-Response Relationship, Drug ; Hydralazines ; Molecular Structure ; P. falciparum ; Parasitic Sensitivity Tests ; Phthalazines - chemical synthesis ; Phthalazines - chemistry ; Phthalazines - pharmacology ; Plasmodium falciparum ; Plasmodium falciparum - drug effects ; Structure-Activity Relationship</subject><ispartof>Bioorganic & medicinal chemistry letters, 2016-07, Vol.26 (14), p.3300-3306</ispartof><rights>2016</rights><rights>Copyright © 2016. Published by Elsevier Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c433t-50192f3272216f7975db6cc8f4d86af9475352e412970c08fb8c2761cf09078f3</citedby><cites>FETCH-LOGICAL-c433t-50192f3272216f7975db6cc8f4d86af9475352e412970c08fb8c2761cf09078f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmcl.2016.05.049$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27261180$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Subramanian, Gowtham</creatorcontrib><creatorcontrib>Babu Rajeev, C.P.</creatorcontrib><creatorcontrib>Mohan, Chakrabhavi Dhananjaya</creatorcontrib><creatorcontrib>Sinha, Ameya</creatorcontrib><creatorcontrib>Chu, Trang T.T.</creatorcontrib><creatorcontrib>Anusha, Sebastian</creatorcontrib><creatorcontrib>Ximei, Huang</creatorcontrib><creatorcontrib>Fuchs, Julian E.</creatorcontrib><creatorcontrib>Bender, Andreas</creatorcontrib><creatorcontrib>Rangappa, Kanchugarakoppal S.</creatorcontrib><creatorcontrib>Chandramohanadas, Rajesh</creatorcontrib><creatorcontrib>Basappa</creatorcontrib><title>Synthesis and in vitro evaluation of hydrazinyl phthalazines against malaria parasite, Plasmodium falciparum</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>[Display omitted]
In this report, we describe the synthesis of 1-(Phthalazin-4-yl)-hydrazine using bronsted acidic ionic liquids and demonstrate their ability to inhibit asexual stage development of human malaria parasite, Plasmodium falciparum. Through computational studies, we short-listed chemical scaffolds with potential binding affinity to an essential parasite protein, dihydroorotate dehydrogenase (DHODH). Further, these compounds were synthesized in the lab and tested against P. falciparum. Several compounds from our library showed inhibitory activity at low micro-molar concentrations with minimal cytotoxic effects. 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In this report, we describe the synthesis of 1-(Phthalazin-4-yl)-hydrazine using bronsted acidic ionic liquids and demonstrate their ability to inhibit asexual stage development of human malaria parasite, Plasmodium falciparum. Through computational studies, we short-listed chemical scaffolds with potential binding affinity to an essential parasite protein, dihydroorotate dehydrogenase (DHODH). Further, these compounds were synthesized in the lab and tested against P. falciparum. Several compounds from our library showed inhibitory activity at low micro-molar concentrations with minimal cytotoxic effects. These results indicate the potential of hydralazine derivatives as reference scaffolds to develop novel antimalarials.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>27261180</pmid><doi>10.1016/j.bmcl.2016.05.049</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Bioorganic & medicinal chemistry letters, 2016-07, Vol.26 (14), p.3300-3306 |
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| subjects | Animals Antimalarials Antimalarials - chemical synthesis Antimalarials - chemistry Antimalarials - pharmacology Bronsted acidic ionic liquids Cell Line Dihydroorotate dehydrogenase Dogs Dose-Response Relationship, Drug Hydralazines Molecular Structure P. falciparum Parasitic Sensitivity Tests Phthalazines - chemical synthesis Phthalazines - chemistry Phthalazines - pharmacology Plasmodium falciparum Plasmodium falciparum - drug effects Structure-Activity Relationship |
| title | Synthesis and in vitro evaluation of hydrazinyl phthalazines against malaria parasite, Plasmodium falciparum |
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