Trypanocidal activity of piperazine-linked bisbenzamidines and bisbenzamidoxime, an orally active prodrug
A series of 32 piperazine-linked bisbenzamidines (and related analogues) were analysed for their in vitro and in vivo trypanocidal activity against a drug-sensitive strain of Trypanosoma brucei brucei and a drug-resistant strain of Trypanosoma brucei rhodesiense. The compounds showed similar potencies against both strains. The most potent compounds were bisbenzamidines substituted at the amidinium nitrogens with a linear pentyl group (8, inhibitory concentration for 50% (IC(50))=1.7-3.0 nM) or cyclic octyl group (17, IC(50)=2.3-4.6 nM). Replacement of the diamidine groups with diamidoxime groups resulted in a prodrug (22) that was effective orally against T. b. brucei-infected mice. Three compounds (7, 11 and 15) provided 100% cure when administered parenterally. The results indicate that the nature of the substituents at the amidinium nitrogens of bisbenzamidines strongly influence their trypanocidal activity.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2007 |
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| Erschienen: |
2007 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
|---|---|
| Enthalten in: |
International journal of antimicrobial agents - 30(2007), 6 vom: 21. Dez., Seite 555-61 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Huang, Tien L [VerfasserIn] |
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| Themen: |
1RTM4PAL0V |
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| Anmerkungen: |
Date Completed 29.01.2008 Date Revised 01.12.2018 published: Print-Electronic Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM174239181 |
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| 100 | 1 | |a Huang, Tien L |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Trypanocidal activity of piperazine-linked bisbenzamidines and bisbenzamidoxime, an orally active prodrug |
| 264 | 1 | |c 2007 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 29.01.2008 | ||
| 500 | |a Date Revised 01.12.2018 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a A series of 32 piperazine-linked bisbenzamidines (and related analogues) were analysed for their in vitro and in vivo trypanocidal activity against a drug-sensitive strain of Trypanosoma brucei brucei and a drug-resistant strain of Trypanosoma brucei rhodesiense. The compounds showed similar potencies against both strains. The most potent compounds were bisbenzamidines substituted at the amidinium nitrogens with a linear pentyl group (8, inhibitory concentration for 50% (IC(50))=1.7-3.0 nM) or cyclic octyl group (17, IC(50)=2.3-4.6 nM). Replacement of the diamidine groups with diamidoxime groups resulted in a prodrug (22) that was effective orally against T. b. brucei-infected mice. Three compounds (7, 11 and 15) provided 100% cure when administered parenterally. The results indicate that the nature of the substituents at the amidinium nitrogens of bisbenzamidines strongly influence their trypanocidal activity | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 7 | |a Benzamidines |2 NLM | |
| 650 | 7 | |a Piperazines |2 NLM | |
| 650 | 7 | |a Prodrugs |2 NLM | |
| 650 | 7 | |a Trypanocidal Agents |2 NLM | |
| 650 | 7 | |a Piperazine |2 NLM | |
| 650 | 7 | |a 1RTM4PAL0V |2 NLM | |
| 700 | 1 | |a Bacchi, Cyrus J |e verfasserin |4 aut | |
| 700 | 1 | |a Kode, Nageswara R |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Qiang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Guangdi |e verfasserin |4 aut | |
| 700 | 1 | |a Yartlet, Nigel |e verfasserin |4 aut | |
| 700 | 1 | |a Rattendi, Donna |e verfasserin |4 aut | |
| 700 | 1 | |a Londono, Indira |e verfasserin |4 aut | |
| 700 | 1 | |a Mazumder, Lakshman |e verfasserin |4 aut | |
| 700 | 1 | |a Vanden Eynde, Jean Jacques |e verfasserin |4 aut | |
| 700 | 1 | |a Mayence, Annie |e verfasserin |4 aut | |
| 700 | 1 | |a Donkor, Isaac O |e verfasserin |4 aut | |
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