کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1359030 981375 2010 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synthesis and antimalarial activities of rhenium bioorganometallics based on the 4-aminoquinoline structure
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Synthesis and antimalarial activities of rhenium bioorganometallics based on the 4-aminoquinoline structure
چکیده انگلیسی

A bioorganometallic approach to malaria therapy led to the discovery of ferroquine (FQ, SSR97193). To assess the importance of the electronic properties of the ferrocenyl group, cyclopentadienyltricarbonylrhenium analogues related to FQ, were synthesized. The reaction of [N-(7-chloro-4-quinolinyl)-1,2-ethanodiamine] with the cyrhetrenylaldehyde complexes (η5-C5H4CHO)Re(CO)3 and [η5-1,2-C5H3(CH2OH)(CHO)]Re(CO)3 produces the corresponding imine derivatives [η5-1,2-C5H3(R)(CHN–CH2CH2NH–QN)]Re(CO)3 R = H 3a; R = CH2OH 3b; QN = N-(7-Cl-4-quinolinyl). Reduction of 3a and 3b with sodium borohydride in methanol yields quantitatively the amine complexes [η5-1,2-C5H3(R)(CH2–NH–CH2CH2NH–QN)]Re(CO)3 R = H 4a; R = CH2OH 4b. To establish the role of the cyrethrenyl moiety in the antimalarial activity of this series, purely organic parent compounds were also synthesized and tested. Evaluation of antimalarial activity measured in vitro against the CQ-resistant strains (W2) and the CQ-susceptible strain (3D7) of Plasmodium falciparum indicates that these cyrhetrene conjugates are less active compared to their ferrocene and organic analogues. These data suggest an original mode-of-action of FQ and ferrocenyl analogues in relationship with the redox pharmacophore.

A series of new 4-aminoquinoline-cyrhetrene derivatives have been synthesized and tested for efficacy against both chloroquine-susceptible and chloroquine-resistant strains of Plasmodium falciparum. To establish the role of the cyrhethrenyl moiety in the antimalarial activity of this series, purely organic parent compounds were also synthesized and tested.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 18, Issue 22, 15 November 2010, Pages 8085–8091
نویسندگان
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