دورية أكاديمية
Synthesis and antiprotozoal activities of benzyl phenyl ether diamidine derivatives.
| العنوان: | Synthesis and antiprotozoal activities of benzyl phenyl ether diamidine derivatives. |
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| المؤلفون: | Patrick DA; Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina, Chapel Hill, NC 27599-7525, USA., Bakunov SA, Bakunova SM, Jones SK, Wenzler T, Barszcz T, Kumar A, Boykin DW, Werbovetz KA, Brun R, Tidwell RR |
| المصدر: | European journal of medicinal chemistry [Eur J Med Chem] 2013 Sep; Vol. 67, pp. 310-24. Date of Electronic Publication: 2013 Jun 25. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Editions Scientifiques Elsevier Country of Publication: France NLM ID: 0420510 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1768-3254 (Electronic) Linking ISSN: 02235234 NLM ISO Abbreviation: Eur J Med Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Paris : Editions Scientifiques Elsevier Original Publication: Paris, S.E.C.T. [etc.] |
| مواضيع طبية MeSH: | Antiprotozoal Agents/*pharmacology , Leishmania donovani/*drug effects , Pentamidine/*analogs & derivatives , Pentamidine/*pharmacology , Phenyl Ethers/*chemical synthesis , Phenyl Ethers/*pharmacology , Plasmodium falciparum/*drug effects , Trypanosoma brucei rhodesiense/*drug effects , Trypanosomiasis/*drug therapy, Animals ; Antiprotozoal Agents/chemical synthesis ; Antiprotozoal Agents/chemistry ; Dose-Response Relationship, Drug ; Mice ; Molecular Structure ; Myoblasts/drug effects ; Parasitic Sensitivity Tests ; Pentamidine/chemical synthesis ; Pentamidine/chemistry ; Phenyl Ethers/chemistry ; Rats ; Structure-Activity Relationship ; Trypanosomiasis/veterinary |
| مستخلص: | Sixty-two cationic benzyl phenyl ether derivatives (36 amidines and 26 prodrugs) were prepared and assayed for activities in vitro and in vivo against Trypanosoma brucei rhodesiense (STIB900), and in vitro against Plasmodium falciparum (K1) and Leishmania donovani axenic amastigotes. 3-Amidinobenzyl 4-amidino-2-iodo-6-methoxyphenyl ether dihydrochloride (55, IC50 = 3.0 nM) and seven other compounds exhibited IC50 values below 10 nM against T. b. rhodesiense in vitro. The 2-bromo-4,4'-diamidino analogue 19 (IC50 = 4.0 nM) and 12 other analogues were more potent than pentamidine (IC50 = 46 nM) against P. falciparum. The 3',4-diamidino-2,6-diiodo analogue 49 (IC50 = 1.4 μM) and two other compounds were more effective than pentamidine (IC50 = 1.8 μM) against L. donovani. A prodrug, 3',4-bis(N″-methoxy)amidino-2-bromo derivative 38, was the most efficacious against trypanosome infected mice, attaining 4/4 cures in four daily 25 mg/kg oral doses, and the 2-chloro-4,4'-diamidine 18 cured 3/4 mice in four daily 5 mg/kg intraperitoneal doses. (Copyright © 2013 Elsevier Masson SAS. All rights reserved.) |
| فهرسة مساهمة: | Keywords: 50% inhibition concentration; ATMS; Antileishmanial; Antiplasmodial; Antiprotozoal; Antitrypanosomal; BPE; Benzyl phenyl ether derivatives; CQ; Diamidines; FMD; HAT; IC(50); MLSR; PMD; PPT; Prodrugs; SI; WHO; World Health Organization; artemisinin; benzyl phenyl ether; chloroquine; furamidine; human African trypanosomiasis; melarsoprol; pentamidine; podophyllotoxin; selectivity index |
| المشرفين على المادة: | 0 (Antiprotozoal Agents) 0 (Phenyl Ethers) 673LC5J4LQ (Pentamidine) |
| تواريخ الأحداث: | Date Created: 20130723 Date Completed: 20140404 Latest Revision: 20130909 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.ejmech.2013.06.033 |
| PMID: | 23871911 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1768-3254 |
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| DOI: | 10.1016/j.ejmech.2013.06.033 |