Evaluation of Ruthenium(II) N-Heterocyclic Carbene Complexes as Enzymatic Inhibitory Agents with Antioxidant, Antimicrobial, Antiparasitical and Antiproliferative Activity

Abstract

A series of [RuCl2(p-cymene)(NHC)] complexes were obtained by reacting [RuCl2(p-cymene)]2 with in situ generated Ag-N-heterocyclic carbene (NHC) complexes. The structure of the obtained complexes was determined by the appropriate spectroscopy and elemental analysis. In addition, we evaluated the biological activities of these compounds as antienzymatic, antioxidant, antibacterial, anticancer, and antiparasitic agents. The results revealed that complexes 3b and 3d were the most potent inhibitors against AchE with IC50 values of 2.52 and 5.06 μM mL−1. Additionally, 3d proved very good antimicrobial activity against all examined microorganisms with IZ (inhibition zone) over 25 mm and MIC (minimum inhibitory concentration) < 4 µM. Additionally, the ligand 2a and its corresponding ruthenium (II) complex 3a had good cytotoxic activity against both cancer cells HCT-116 and HepG-2, with IC50 values of (7.76 and 11.76) and (4.12 and 9.21) μM mL−1, respectively. Evaluation of the antiparasitic activity of these complexes against Leishmania major promastigotes and Toxoplasma gondii showed that ruthenium complexes were more potent than the free ligand, with an IC50 values less than 1.5 μM mL−1. However, 3d was found the best one with SI (selectivity index) values greater than 5 so it seems to be the best candidate for antileishmanial drug discovery program, and much future research are recommended for mode of action and in vivo evaluation. In general, Ru-NHC complexes are the most effective against L. major promastigotes.

Synthesis of Novel N-Heterocyclic Carbene-Ruthenium (II) Complexes, “Precious” Tools with Antibacterial, Anticancer and Antioxidant Properties

“…Overall, the ABTS scavenging activity pattern of the Ru-NHC complexes can be graded in the following order: RANHC-III > -IV > -V > -I > -II > -VI . These activities are higher than those reported in studies on similar complexes [ 37 ].…”

“…The other Ru-NCH complexes showed IC 50 values higher than 100 µM against both the adopted normal cells. Similar published complexes showed anticancer activity against different cancer cells, but with higher IC 50 values or higher cytotoxic effects against the adopted normal cell lines [ 36 , 37 ].…”

“…We also determined the minimum bactericidal concentration (MBC), resulting in greater than 100 µg/mL for all the complexes. Comparable or lower MIC values against S. aureus were recently published for similar complexes, even though they were quite toxic against the HepG2 cells [37]. [a] Minimum inhibitory concentration.…”

Synthesis, DFT calculations, and investigation of catalytic and biological activities of back‐bond functionalized re‐NHC‐Cu complexes

“…[68][69][70][71] These findings support our previous claim that NHC complexes of potent antileishmanial and antitoxoplasmal activity. 70,71 T A B L E 4 Antioxidant activity of 3a-e complexes assessed by DPPH, ABTS antiradical scavenging power, and β-carotene bleaching test presented by their IC 50 in μM mL À1 of mean ± SD.…”

“…These results agree with our previous finding for the ability of NHC complex as a relatively active against enzymes. 70…”