Improved antiparasitic activity by incorporation of organosilane entities into half-sandwich ruthenium(ii) and rhodium(iii) thiosemicarbazone complexes

Abstract

A series of ferrocenyl- and aryl-functionalised organosilane thiosemicarbazone compounds was obtained via a nucleophilic substitution reaction with an amine-terminated organosilane. The thiosemicarbazone (TSC) ligands were further reacted with either a ruthenium dimer [(η(6-i)PrC6H4Me)Ru(μ-Cl)Cl]2 or a rhodium dimer [(Cp*)Rh(μ-Cl)Cl]2 to yield a series of cationic mono- and binuclear complexes. The thiosemicarbazone ligands, as well as their metal complexes, were characterised using NMR and IR spectroscopy, and mass spectrometry. The molecular structure of the binuclear ruthenium(ii) complex was determined by single-crystal X-ray diffraction analysis. The thiosemicarbazones and their complexes were evaluated for their in vitro antiplasmodial activities against the chloroquine-sensitive (NF54) and chloroquine-resistant (Dd2) Plasmodium falciparum strains, displaying activities in the low micromolar range. Selected compounds were screened for potential β-haematin inhibition activity, and it was found that two Rh(iii) complexes exhibited moderate to good inhibition. Furthermore, the compounds were screened for their antitrichomonal activities against the G3 Trichomonas vaginalis strain, revealing a higher percentage of growth inhibition for the ruthenium and rhodium complexes over their corresponding ligand.

Organometallic Conjugates of the Drug Sulfadoxine for Combatting Antimicrobial Resistance

“…This demonstrates that conjugation of organometallic groups to ad rug can alter its biological target, as notedb yothers. [15,21,22,[47][48][49][50][51][52][53][54][55][56] All the complexes studied contain ar eactive metalÀCl bond that readily underwent aquation, although the rates varied widely,b eing slowest for the complexes with Cp xbiph ligands with half-lives of > 2h (4, 7 and 14), and fastest (minutes)f or Cp* complexes (2 and 9). From this library,s everalc omplexes are promising forf urther development as antiparasitica nd antitubercular agents.…”

Cyclopalladated organosilane–tethered thiosemicarbazones: novel strategies for improving antiplasmodial activity

“…The dithiocarbamates and the TSCs (1a-3a) are known compounds which were prepared following published methods. 26,33,34 The dithiocarbamates were prepared via the Schiff-base condensation of methyl hydrazinecarbodithioate 35 with either acetylferrocene or 3,4dichloroacetophenone. 33,34 The cyclopalladated complexes (4-6) were prepared via C-H activation of the cyclopentadienyl or aryl rings of the ferrocenyl-and aryl-derived TSCs, respectively, when reacted with the palladium precursor cis-[PdCl 2 (PTA) 2 ] in the presence of triethylamine as the base (Scheme 1).…”

“…All reagents and solvents were obtained from commercial sources (Sigma-Aldrich, Merck, Kimix, UkrOrgSyntez and FCH group) and, unless otherwise stated, were used as received. The Schiff-base dithiocarbamates, 33,42 TSCs (1a, 2a, 3a) 26 and PdCl 2 (PTA) 2 43 were prepared following literature methods.…”

Exploring Ruthenium-based organometallic inhibitors against Plasmodium Calcium Dependent Kinase 2 (PfCDPK2): a combined ensemble docking, QM paramterization and molecular dynamics study

“…Recent efforts in similar direction have shown that the kinetically inert metal center (Ru, Rh, and Ir) could complement with organic fragment and serve as "hyper-valent carbon" which is not involved in any direct interactions but plays important role in building 3D space (Debreczeni et al, 2006;Meggers, 2009). Earlier, a plethora of literature has claimed the antimalarial properties of transition metalbased compounds (Adams et al, 2015(Adams et al, , 2013Barbosa et al, 2014;Chellan et al, 2014;Glans et al, 2012). One of the potential successes is the antimalarial activity of ferroquine, a chloroquinederived iron-based organometallic compound which has proceeded to Phase IIB clinical trials (Biot, Castro, Botté, & Navarro, 2012;Dubar et al, 2011Dubar et al, , 2013Held et al, 2015).…”