Computational simulations of Ru(II) complexes with coordinated jaborandi ligands and their potential for interaction with Trypanosoma cruzi proteases

Chagas disease is a parasitic infection caused by the protozoan Trypanosoma cruzi, in which conventional treatment is based on medications such as benznidazole and nifurtimox, which have limitations, such as side effects and parasitic resistance. Thus, some metallopharmaceuticals have been studied as potential therapeutic agents, in this sense, the present in silico study predicts the interaction capacity of Ru(II) complexes formed with jaborandi alkaloid ligands, against the protozoan sterol 14α-demethylase and cruzain proteases. The physicochemical properties, ADME-Tox, druglikeness and biological activity of the in silico complexes, predicted from website databases, were also evaluated. The complexes with the best binding affinities after molecular docking were those with the target cruzain, with emphasis on [RuNO(bipy)2IPS]3+, [RuCl(bipy)2PS]+, [RuNO(bipy)2PS]3 + and [RuCl(bipy)2IPS]+, carrying out important chemical interactions with the amino acid residues Cys25, Gln19, Gly66, Gly23 and Trp26. Only [RuCl(bipy)2PS]+, [RuCl(bipy)2IPS]+ and [RuCl(bipy)2EPS]+ showed activities for antiprotozoal (Trypanosoma), anticarcinogenic and antitoxic actions. The complexes under study have good oral bioavailability, lipophilicity, aqueous solubility, permeability, absorption and absence of neurotoxicity. However, the proposed compounds still need to undergo in vitro and in vivo laboratory tests to carry out new studies.