Triazolyl Ru(II), Os(II), and Ir(III) complexes as potential HIV-1 inhibitors.

Abstract

Infection by the human immunodeficiency virus, which gives rise to acquired immunodeficiency syndrome, is still a major global health challenge, with millions of people being affected. The use of combination antiretroviral therapy has been a great success, leading to reduced mortality rates over the years. Although successful, these drugs are associated with various side effects, necessitating the development of new treatment strategies. This study investigated three metal-based complexes that were previously shown to possess some anticancer activity. The complexes were investigated against three pseudoviruses, which consisted of HIV-1 subtype C (CAP 210 and Du 156) and subtype A (Q 23). These complexes inhibited viral entry at low micromolar concentrations, with IC50 values ranging from 5.34 to 7.41µM for N-aryl-1H-1,2,3-triazole-based cyclometalated ruthenium-(II) (A), 2.35-8.09µM for N-aryl-1H-1,2,3-triazole-based cyclometalated iridium-(III) (B) and 2.59-4.18µM for N-aryl-1H-1,2,3-triazole-based cyclometalated osmium-(II) complex (C). This inhibition was significant, with no significant inhibition from the ligand alone at similar concentrations. Additionally, these concentrations were non-toxic to mammalian cells. The complexes were further analysed for their potential mechanism of action using in silico docking (Maestro 12.2), which indicated that the activity is potentially due to their interaction with the CCR5 co-receptor. The predicted interaction involved amino acids (Glu 283, Tyr 251 and Tyr 108) that are essential for the interaction of the chemokine receptor with viral gp120.