Synthesis and antimicrobial study of organoiridium amido-sulfadoxine complexes

Abstract

Two new ligands, pyridylamido-sulfadoxine (L1) and quinolylamido-sulfadoxine (L2), were prepared by the reaction of the antimicrobial sulfadrug, sulfadoxine, with either 2-picolinic acid or 2-quinaldic acid. Subsequent reaction with a [CpxIrCl2]2 dimer (where Cpx = pentamethylcyclopentadiene, tetramethylphenylcyclopentadiene or tetramethylbiphenylcyclopentadiene) yielded six new amidosulfadoxine-derivatized iridium complexes (C1-C6) in moderate to good yields, where the ligands act as N,N’-bidentate chelators. Proton and carbon NMR spectroscopy, mass spectrometry and HPLC data were used to characterize and confirm the purity of all compounds. Aquation chemistry studies on the complexes revealed slow water substitution of the chlorido ancillary ligand. The inhibitory activities of complexes C1-C6 were determined against Mycobacterium tuberculosis (Mtb) H37Rv and Plasmodium falciparum (Pf) strains, 3D7, Dd2 and HB3, as well as the HEK cell line. The ligands showed no appreciable antimicrobial activity, with most of the complexes exhibiting weak to moderate inhibition of Pf and Mtb. However, one complex (C6) displayed potent activity against Pf 3D7 (IC50 of 0.975 µM) and the multidrug-resistant Pf Dd2 (IC50 of 0.766 µM).