Synthesis, cytotoxicity and antimalarial activity of ferrocenyl amides of 4-aminoquinolines

D N’Da David; C Breytenbach Jaco; J Smith Peter; Carmen Lategan

doi:10.1055/s-0031-1296337

Arzneimittelforschung, Table of Contents

Arzneimittelforschung 2010; 60(10): 627-635
DOI: 10.1055/s-0031-1296337

Antibiotics · Antimycotics · Antiparasitics · Antiviral Drugs · Chemotherapeutics · Cytostatics

Editio Cantor Verlag Aulendorf (Germany)

Synthesis, cytotoxicity and antimalarial activity of ferrocenyl amides of 4-aminoquinolines

D N’Da David

¹Pharmaceutical Chemistry, North-West University, Potchefstroom, South Africa

,

C Breytenbach Jaco

¹Pharmaceutical Chemistry, North-West University, Potchefstroom, South Africa

,

J Smith Peter

²Pharmacology, University of Cape Town, Groote Schuur Hospital, Observatory, South Africa

,

Carmen Lategan

²Pharmacology, University of Cape Town, Groote Schuur Hospital, Observatory, South Africa

› Author Affiliations

Abstract

Series of 4-aminoquinolines bearing an amino side chain linked to the ferrocene moiety through an amide bond were synthesized and evaluated for their antimalarial activity against both chloro-quine-sensitive (D10, CQ-S) and chloro-quine-resistant (Dd2, CQ-R) strains of Plasmodium falciparum. They were also tested for cytotoxicity against Chinese Hamster Ovarian (CHO) cells. Amide 12 featuring propyl side chain linked to the ferrocene ring was the most active of all tested compounds. With an IC₅₀ value of 0.08 µg/mL, this amide showed 1.5-fold higher activity than chloroquine diphosphate (IC₅₀ = 0.12 µg/mL) against the resistant strain, with a selectivity index of 550 indicating its high selectivity towards the parasite. Derivatives which were equipotent against both strains also showed up to ten-fold increase in activity compared to primaquine.

Key words

4-Aminoquinolines - Antimalarial activity - Cytotoxicity - Ferrocene - Plasmodium falciparum

Full Text

References

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