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Synthesis and biological activity of cymantrene and cyrhetrene 4-aminoquinoline conjugates against malaria, leishmaniasis, and trypanosomiasis.

Glans, Lotta LU ; Hu, Wanning; Jöst, Christian; de Kock, Carmen; Smith, Peter J; Haukka, Matti; Bruhn, Heike; Schatzschneider, Ulrich and Nordlander, Ebbe LU (2012) In Dalton Transactions 41(21). p.6443-6450
Abstract
Organometallic analogues of chloroquine show promise as new antimalarial agents capable of overcoming resistance to the parent drug chloroquine. Here, the synthesis and characterization of three new cymantrene (CpMn(CO)(3)) and cyrhetrene (CpRe(CO)(3)) 4-aminoquinoline conjugates with either an amine or amide linker are reported. The antimalarial activity of the new organometallic conjugates N-(2-(7-chloroquinolin-4-ylamino)ethyl)-4-cymantrenylbutanamide (), N-(2-(7-chloroquinolin-4-ylamino)ethyl)-4-cyrhetrenylbutanamide () and N-(7-chloroquinolin-4-yl)-N'-(cymantrenylmethyl)ethane-1,2-diamine () was evaluated against a chloroquine-sensitive (CQS) and a chloroquine-resistant strain (CQR) of the malaria parasite Plasmodium falciparum. The... (More)
Organometallic analogues of chloroquine show promise as new antimalarial agents capable of overcoming resistance to the parent drug chloroquine. Here, the synthesis and characterization of three new cymantrene (CpMn(CO)(3)) and cyrhetrene (CpRe(CO)(3)) 4-aminoquinoline conjugates with either an amine or amide linker are reported. The antimalarial activity of the new organometallic conjugates N-(2-(7-chloroquinolin-4-ylamino)ethyl)-4-cymantrenylbutanamide (), N-(2-(7-chloroquinolin-4-ylamino)ethyl)-4-cyrhetrenylbutanamide () and N-(7-chloroquinolin-4-yl)-N'-(cymantrenylmethyl)ethane-1,2-diamine () was evaluated against a chloroquine-sensitive (CQS) and a chloroquine-resistant strain (CQR) of the malaria parasite Plasmodium falciparum. The cymantrene complex with an amine linker () showed good activity against the CQS strain but was inactive against the CQR strain. In contrast, cymantrene and cyrhetrene compounds with an amide linker were active against both the CQS and the CQR strain. In addition, the antibacterial, anti-trypanosomal and anti-leishmanial activity of the compounds was evaluated. Compound showed submicromolar activity against Trypanosoma brucei at a concentration where the toxicity to normal human cells is low. No significant effect was noticed on the exchange of manganese for rhenium in the CpM(CO)(3) moiety in any of the biological assays. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Dalton Transactions
volume
41
issue
21
pages
6443 - 6450
publisher
Royal Society of Chemistry
external identifiers
  • wos:000303775000013
  • pmid:22421887
  • scopus:84862882921
ISSN
1477-9234
DOI
10.1039/c2dt30077j
language
English
LU publication?
yes
id
e9474b31-8fe1-4015-9b5c-dda7a6f8a3bb (old id 2431735)
date added to LUP
2012-04-12 16:57:12
date last changed
2017-08-13 03:07:40
@article{e9474b31-8fe1-4015-9b5c-dda7a6f8a3bb,
  abstract     = {Organometallic analogues of chloroquine show promise as new antimalarial agents capable of overcoming resistance to the parent drug chloroquine. Here, the synthesis and characterization of three new cymantrene (CpMn(CO)(3)) and cyrhetrene (CpRe(CO)(3)) 4-aminoquinoline conjugates with either an amine or amide linker are reported. The antimalarial activity of the new organometallic conjugates N-(2-(7-chloroquinolin-4-ylamino)ethyl)-4-cymantrenylbutanamide (), N-(2-(7-chloroquinolin-4-ylamino)ethyl)-4-cyrhetrenylbutanamide () and N-(7-chloroquinolin-4-yl)-N'-(cymantrenylmethyl)ethane-1,2-diamine () was evaluated against a chloroquine-sensitive (CQS) and a chloroquine-resistant strain (CQR) of the malaria parasite Plasmodium falciparum. The cymantrene complex with an amine linker () showed good activity against the CQS strain but was inactive against the CQR strain. In contrast, cymantrene and cyrhetrene compounds with an amide linker were active against both the CQS and the CQR strain. In addition, the antibacterial, anti-trypanosomal and anti-leishmanial activity of the compounds was evaluated. Compound showed submicromolar activity against Trypanosoma brucei at a concentration where the toxicity to normal human cells is low. No significant effect was noticed on the exchange of manganese for rhenium in the CpM(CO)(3) moiety in any of the biological assays.},
  author       = {Glans, Lotta and Hu, Wanning and Jöst, Christian and de Kock, Carmen and Smith, Peter J and Haukka, Matti and Bruhn, Heike and Schatzschneider, Ulrich and Nordlander, Ebbe},
  issn         = {1477-9234},
  language     = {eng},
  number       = {21},
  pages        = {6443--6450},
  publisher    = {Royal Society of Chemistry},
  series       = {Dalton Transactions},
  title        = {Synthesis and biological activity of cymantrene and cyrhetrene 4-aminoquinoline conjugates against malaria, leishmaniasis, and trypanosomiasis.},
  url          = {http://dx.doi.org/10.1039/c2dt30077j},
  volume       = {41},
  year         = {2012},
}