Synthesis and antimalarial evaluation of new 1,4-bis(3-aminopropyl)piperazine derivatives
Synthesis and evaluation of the activity of a new family of 1,4-bis(3-aminopropyl)piperazine derivatives against a chloroquine-resistant strain of Plasmodium falciparum, and as inhibitors of beta-hematin formation, are described. The highest antimalarial activities were obtained for compounds displa...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2003-11, Vol.13 (21), p.3783-3787 |
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| container_end_page | 3787 |
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| container_issue | 21 |
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| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 13 |
| creator | RYCKEBUSCH, Adina DEPREZ-POULAIN, Rébecca DEBREU-FONTAINE, Marie-Ange VANDAELE, Richard MOURAY, Elisabeth GRELLIER, Philippe SERGHERAERT, Christian |
| description | Synthesis and evaluation of the activity of a new family of 1,4-bis(3-aminopropyl)piperazine derivatives against a chloroquine-resistant strain of Plasmodium falciparum, and as inhibitors of beta-hematin formation, are described. The highest antimalarial activities were obtained for compounds displaying the highest predicted vacuolar accumulation ratios and the best potencies as inhibitors of beta-hematin formation. The most potent compound displayed an activity 3-fold better than chloroquine for a comparable selectivity index upon MRC-5 cells. Therefore, in this series, the replacement of the 7-chloroquinoline group can constitute a strong rationale for further investigation. |
| doi_str_mv | 10.1016/j.bmcl.2003.07.008 |
| format | Article |
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The highest antimalarial activities were obtained for compounds displaying the highest predicted vacuolar accumulation ratios and the best potencies as inhibitors of beta-hematin formation. The most potent compound displayed an activity 3-fold better than chloroquine for a comparable selectivity index upon MRC-5 cells. Therefore, in this series, the replacement of the 7-chloroquinoline group can constitute a strong rationale for further investigation.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2003.07.008</identifier><identifier>PMID: 14552779</identifier><language>eng</language><publisher>Oxford: Elsevier</publisher><subject>Algorithms ; Animals ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antimalarials - chemical synthesis ; Antimalarials - pharmacology ; Antiparasitic agents ; Biological and medical sciences ; Cell Line ; Cell Survival - drug effects ; Chloroquine - pharmacology ; Drug Resistance ; Hemeproteins - antagonists & inhibitors ; Hemeproteins - biosynthesis ; Humans ; Indicators and Reagents ; Medical sciences ; Miscellaneous ; Pharmacology. 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The highest antimalarial activities were obtained for compounds displaying the highest predicted vacuolar accumulation ratios and the best potencies as inhibitors of beta-hematin formation. The most potent compound displayed an activity 3-fold better than chloroquine for a comparable selectivity index upon MRC-5 cells. Therefore, in this series, the replacement of the 7-chloroquinoline group can constitute a strong rationale for further investigation.</description><subject>Algorithms</subject><subject>Animals</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antimalarials - chemical synthesis</subject><subject>Antimalarials - pharmacology</subject><subject>Antiparasitic agents</subject><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>Cell Survival - drug effects</subject><subject>Chloroquine - pharmacology</subject><subject>Drug Resistance</subject><subject>Hemeproteins - antagonists & inhibitors</subject><subject>Hemeproteins - biosynthesis</subject><subject>Humans</subject><subject>Indicators and Reagents</subject><subject>Medical sciences</subject><subject>Miscellaneous</subject><subject>Pharmacology. Drug treatments</subject><subject>Piperazines - chemical synthesis</subject><subject>Piperazines - pharmacology</subject><subject>Plasmodium falciparum - drug effects</subject><subject>Structure-Activity Relationship</subject><subject>Vacuoles - drug effects</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE1LxDAQhoMo7rr6BzxIL4qCrZM0adqjLH7BggcV9BSSNMUs6YdJu7L-ervswh6GuTzvy8yD0DmGBAPO7paJqrVLCECaAE8A8gM0xTSjcUqBHaIpFBnEeUE_J-gkhCUApkDpMZpgyhjhvJiir7d103-bYEMkm3Kc3tbSSW-li8xKukH2tm2itooa8xvhWxorG67TWNa2aTvfdmt309nOePlnGxOVxtvVGFmZcIqOKumCOdvtGfp4fHifP8eL16eX-f0i1mnB-phJJXPOSc4ynuOS6ZQpQirKVU5YRZk2nCgslSZVxTHmCgPXIwxlRlSqWTpDV9ve8ZqfwYRe1DZo45xsTDsEwRnPMGYbkGxB7dsQvKlE58dn_VpgEBuhYik2QsVGqAAuRqFj6GLXPqjalPvIzuAIXO4AGbR0lZeNtmHPMcwzlhXpPxS0f9k</recordid><startdate>20031103</startdate><enddate>20031103</enddate><creator>RYCKEBUSCH, Adina</creator><creator>DEPREZ-POULAIN, Rébecca</creator><creator>DEBREU-FONTAINE, Marie-Ange</creator><creator>VANDAELE, Richard</creator><creator>MOURAY, Elisabeth</creator><creator>GRELLIER, Philippe</creator><creator>SERGHERAERT, Christian</creator><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20031103</creationdate><title>Synthesis and antimalarial evaluation of new 1,4-bis(3-aminopropyl)piperazine derivatives</title><author>RYCKEBUSCH, Adina ; DEPREZ-POULAIN, Rébecca ; DEBREU-FONTAINE, Marie-Ange ; VANDAELE, Richard ; MOURAY, Elisabeth ; GRELLIER, Philippe ; SERGHERAERT, Christian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c395t-5aba8772856781d5c35b22f47b825f45ce72b1abc2ff7117b107c8560d62b3c53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Algorithms</topic><topic>Animals</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antimalarials - chemical synthesis</topic><topic>Antimalarials - pharmacology</topic><topic>Antiparasitic agents</topic><topic>Biological and medical sciences</topic><topic>Cell Line</topic><topic>Cell Survival - drug effects</topic><topic>Chloroquine - pharmacology</topic><topic>Drug Resistance</topic><topic>Hemeproteins - antagonists & inhibitors</topic><topic>Hemeproteins - biosynthesis</topic><topic>Humans</topic><topic>Indicators and Reagents</topic><topic>Medical sciences</topic><topic>Miscellaneous</topic><topic>Pharmacology. 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| ispartof | Bioorganic & medicinal chemistry letters, 2003-11, Vol.13 (21), p.3783-3787 |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Algorithms Animals Antibiotics. Antiinfectious agents. Antiparasitic agents Antimalarials - chemical synthesis Antimalarials - pharmacology Antiparasitic agents Biological and medical sciences Cell Line Cell Survival - drug effects Chloroquine - pharmacology Drug Resistance Hemeproteins - antagonists & inhibitors Hemeproteins - biosynthesis Humans Indicators and Reagents Medical sciences Miscellaneous Pharmacology. Drug treatments Piperazines - chemical synthesis Piperazines - pharmacology Plasmodium falciparum - drug effects Structure-Activity Relationship Vacuoles - drug effects |
| title | Synthesis and antimalarial evaluation of new 1,4-bis(3-aminopropyl)piperazine derivatives |
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