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

Glans, LottaLund University,Lunds universitet,Kemisk fysik,Enheten för fysikalisk och teoretisk kemi,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Chemical Physics,Physical and theoretical chemistry,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH (författare)

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.

Hu, Wanning (författare)
Jöst, Christian (författare)
de Kock, Carmen (författare)
Smith, Peter J (författare)
Haukka, Matti (författare)
Bruhn, Heike (författare)
Schatzschneider, Ulrich (författare)
Nordlander, EbbeLund University,Lunds universitet,Kemisk fysik,Enheten för fysikalisk och teoretisk kemi,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Chemical Physics,Physical and theoretical chemistry,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH(Swepub:lu)ook1-eno (författare)
Kemisk fysikEnheten för fysikalisk och teoretisk kemi (creator_code:org_t)

Ingår i:Dalton Transactions: Royal Society of Chemistry (RSC)41:21, s. 6443-64501477-92341477-9226

Av författaren/redakt...: Glans, Lotta; Hu, Wanning; Jöst, Christian; de Kock, Carmen; Smith, Peter J; Haukka, Matti; visa fler...; Bruhn, Heike; Schatzschneider, ...; Nordlander, Ebbe; visa färre...

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