Organometallic Conjugates of the Drug Sulfadoxine for Combatting Antimicrobial Resistance

ORCID

Kirkwood M. Land: 0000-0001-5951-9630

Document Type

Article

Publication Title

Chemistry: A Euoprean Journal

Department

Biological Sciences

Volume

24

DOI

10.1002/chem.201801090

First Page

10078

Last Page

10090

Publication Date

4-13-2018

Abstract

Fourteen novel arene RuII, and cyclopentadienyl (Cpx) RhIII and IrIII complexes containing an N ,N ′‐chelated pyridylimino‐ or quinolylimino ligand functionalized with the antimalarial drug sulfadoxine have been synthesized and characterized, including three by X‐ray crystallography. The rhodium and iridium complexes exhibited potent antiplasmodial activity with IC50 values of 0.10–2.0 μm in either all, or one of the three Plasmodium falciparum assays (3D7 chloroquine sensitive, Dd2 chloroquine resistant and NF54 sexual late stage gametocytes) but were only moderately active towards Trichomonas vaginalis . They were active in both the asexual blood stage and the sexual late stage gametocyte assays, whereas the clinical parent drug, sulfadoxine, was inactive. Five complexes were moderately active against Mycobacterium tuberculosis (IC50<6.3 μm ), while sulfadoxine showed no antitubercular activity. An increase in the size of both the Cpx ligand and the aromatic imino substituent increased hydrophobicity, which resulted in an increase in antiplasmodial activity.

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