Biomolecular Interactions of Cytotoxic Ruthenium Compounds with Thiosemicarbazone or Benzothiazole Schiff Base Chelates

Abstract

Herein we illustrate the formation and characterization of new paramagnetic ruthenium compounds, trans-P-[RuCl(PPh 3 ) 2 (pmt)]Cl(1)Agarose gel electrophoresis experiments of the metal compounds illustrated dose-dependent binding to gDNA by 1-3, while methylene blue competition assays suggested that 1 and 2 are also DNA intercalators. Assessment of the effects of the compounds on topoisomerase function indicated that 1-3 are capable of inhibiting topoisomerase I activity in terms of the ability to nick supercoiled plasmid DNA. The cytotoxic activities of the metal complexes were determined against a range of cancer cell lines versus a nontumorigenic control cell line, and the complexes were, in general, more cytotoxic towards the cancer cells, displaying IC 50 values in the low micromolar range. Time-dependent stability studies showed that in the presence of strong nucleophilic species (such as DMSO), the chloride co-ligands of 1-3 are rapidly substituted by the former as proven by the suppression of the substitution reactions in the presence of an excess amount of chloride ions. The metal complexes are significantly stable in both DCM and an aqueous phosphate buffer containing 2 % DMSO.

Synthesis, characterization, biomolecular interactions, molecular docking, and in vitro and in vivo anticancer activities of novel ruthenium(III) Schiff base complexes

“…The obtained results demonstrated that the studied complexes bind to IIA and IIIA sites with moderate affinity (K b = 10 4 M − 1 ) without preference for any protein binding site. Similar observations were reported for other Ru(III) complexes with Schiff base chelates[38].3.4. Molecular docking3.4.1.…”

Exploring the Biomolecular and Cytotoxic Activities of Novel Rhenium(I) Compounds with 2‐Aminoguanidine‐Derived Schiff Bases

“…The stabilities of the rhenium(I) complexes were analysed in dimethyl sulfoxide (DMSO) and aqueous phosphate saline buffer (PBS), respectively. [17] A 1.0 mM sample solution of each metal complex was prepared in DMSO. The standardized sample solutions prepared in DMSO were monitored for 24 h after 1 h data collection intervals at 38 °C, using UV-vis spectrophotometry.…”

“…electrostatic and hydrogen-bonding interactions) leading to DNA groove binding. [16][17] PGM compounds with lower coordination numbers generally stack in between the DNA base pairs where planar aromatic chromophores interact via DNA intercalation while selected PGMs can directly bond to DNA base pairs. [18][19] Thus, the intrinsic structural features of a metal complex and the degree of Lewis acidity for its metal centre can bring about controlled cell death by halting the rapid mutation of cellular cancerous DNA.…”

“…The stabilities of the rhenium(I) complexes were analysed in dimethyl sulfoxide (DMSO) and aqueous phosphate saline buffer (PBS), respectively [17] . A 1.0 mM sample solution of each metal complex was prepared in DMSO.…”

“…The high steric demands of octahedral metallated species generally prefer non‐directional bonding ( viz . electrostatic and hydrogen‐bonding interactions) leading to DNA groove binding [16–17] . PGM compounds with lower coordination numbers generally stack in between the DNA base pairs where planar aromatic chromophores interact via DNA intercalation while selected PGMs can directly bond to DNA base pairs [18–19] .…”