Molecular docking of rutenum complex with epiisopyloturin and nitric oxide against nucleoside diphosphate kinase protein Leishmania

Abstract

Leishmaniasis is an infectious disease that affects both animals and humans, caused by flagellated parasites belonging to the genus Leishmania may present in different clinical forms depending on the infecting strain and the immune reaction of the host. The disease is estimated to reach about 700,000 to 1 million people, causing the deaths of 20 to 30,000 individuals annually. Thus, the present study aims to perform a molecular coupling simulation of the ruthenium complex with epiisopiloturin and nitric oxide against the protein Nucleoside diphosphate kinase from Leishmania amazonensis. The NDK 3D molecule was extracted from the PDB nucleic proteins and acids database. The 3D molecular structure of the Epiruno2 complex was designed using gaussview 5.0 software. The NDK target and Epiruno2 complex were prepared for docking simulations, where NDK was considered rigid and Epiruno2 was considered flexible. The Epiruno2 complex presented a good molecular affinity rate with the target protein, making it attractive for experimental trials in laboratories for Leishmania's NDK protein and NDKs of other pathogens, however, the drug miltefosin presented low molecular affinity for the same target, corroborating studies presented in the literature on the reduced efficacy of current drugs against leishmaniosis.

An Overview of the Potential Medicinal and Pharmaceutical Properties of Ru(II)/(III) Complexes

“…A ruthenium(II) complex 69 (EPIRUNO 2 ) (Figure 28) was also studied as a potential drug for the parasitic disease leishmaniasis [125]. Araújo et al [126] performed molecular docking of a complex with imidazole alkaloid abundant from the leaves of Pilocarpus microphyllus, epiisopiloturine (EPI) and nitrogen(IV) oxide ( 69) in nucleoside diphosphate kinase (NDK) from Leishmania amazonensis. The results were compared against a known drug, miltefosine.…”

Molecular Docking and Evaluation of Antileishmania Activity of a Ruthenium Complex with Epiisopiloturine and Nitric Oxide

“…Molecular docking between the 5c7p protein and the Epiruno 2 complex formed three hydrogen bridges at amino acids Arg104, Asn114 and Ser98 (Figure 2) and showed a bind G energy of −8.22 Kcal•mol −1 and an inhibition constant of 935.7 nM (Table 1). These results are promising against this indispensable protein for the maintenance of intracellular nucleoside triphosphate (NTP) levels [35]. They carry the γ-phosphoryl group from an NTP to a nucleoside di- The 1ezr protein can be identified in free extracts of Leishmania cells, is also present in several parasitic protozoa.…”

Leishmaniasis: effect of enalaprilat on the production of (ON) and cytokines in vitro

“…Leishmaniasis represent a complex of infectious and parasitic diseases transmitted to humans by the Phlebotomines carried out by the mosquitoes of the genus Phlebotomus caused by protozoa of the genus Leishmania (Brasil 2010a;Araújo et al 2020).…”