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

Ibrahim S Al Nasr; Waleed S Koko; Tariq A Khan; Nevin Gürbüz; Ismail Özdemir; Naceur Hamdi

doi:10.3390/molecules28031359

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

Molecules. 2023 Jan 31;28(3):1359. doi: 10.3390/molecules28031359.

Authors

Ibrahim S Al Nasr^{1

2}, Waleed S Koko², Tariq A Khan³, Nevin Gürbüz^{4

5}, Ismail Özdemir^{4

5}, Naceur Hamdi⁶

Affiliations

¹ Department of Biology, College of Science and Arts, Qassim University, Unaizah 51911, Saudi Arabia.
² Department of Science Laboratories, College of Science and Arts, Qassim University, Ar Rass 51921, Saudi Arabia.
³ Department of Clinical Nutrition, College of Applied Health Sciences, Qassim University, Ar Rass 51921, Saudi Arabia.
⁴ Department of Chemistry, Faculty of Science and Art, İnönü University, Malatya 44280, Turkey.
⁵ Catalysis Research and Application Center, İnönü University, Malatya 44280, Turkey.
⁶ Department of Chemistry, College of Science and Arts at ArRass, Qassim University, Ar Rass 51921, Saudi Arabia.

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.

Keywords: 5,6-dimethylbenzimidazolium salts; HCT-116; HepG-2; Leishmania; N-Heterocyclic carbene; Toxoplasma; antimicrobial; antioxidant; enzyme inhibition; ruthenium.

MeSH terms

Anti-Infective Agents* / pharmacology
Antineoplastic Agents* / chemistry
Antineoplastic Agents* / pharmacology
Antioxidants / pharmacology
Coordination Complexes* / chemistry
Coordination Complexes* / pharmacology
Ligands
Ruthenium* / chemistry
Ruthenium* / pharmacology

Substances

Ruthenium
4-cymene
Antioxidants
carbene
Ligands
Anti-Infective Agents
Antineoplastic Agents
Coordination Complexes

Grants and funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript except the suppot for the project number (QU-IF-02-02-27782) from Deputyship for Research& Innovation, Ministry of Education, Saudi Arabia.