Trypanocidal Effect of Nano MOFs-EP on Circulating Forms of Trypanosoma cruzi

Abstract

Background: Chagas disease caused by the parasite Trypanosoma cruzi is considered a neglected disease in several countries. One of the main problems about this disease is the lack of an effective treatment and the absence of adverse effects. T. cruzi, like most pathogenic fungi and yeasts, require specific sterols to maintain viability and proliferative capacity during their life cycle. However, the oxidation of this molecule to ergosterol peroxide has shown several biological effects, including its trypanocidal activity.
 Methods: We have synthesized MOFs nanoparticles as carrier system coupled to ergosterol peroxide (MOFs-EP) and we have studied its effect on the circulating forms of the T. cruzi parasite.
 Results: MOFs-EP possess an efficient trypanocidal activity at much lower inhibitory concentrations (ng/mL) that the concentrations shown by ergosterol peroxide (g/mL) when administered unconjugated form.
 Conclusion: Our results open a new possibility in the biomedical application of MOFs and ergosterol peroxide in the search for new options for the treatment of Chagas disease.

Efficacy of a Zn-based metalorganic framework doped with benznidazole on acute experimental Trypanosoma cruzi infection

“…The characterization of the BNZ@Zn-MOF allowed to con rm its correct synthesis, the main characteristics of the Zn(II) polymer are its formation through two organic linkers, 4,4'-bipyridyl and acetate, which in their crystallization present a linear structure in the form of a nanotube, a triclinic system and a P-1 space group, describes a crystalline structure characterized by no particular symmetry in its axes and angles, with no particular symmetry constraint on the arrangement of atoms in the crystal lattice [9]. The doping of MOF with BNZ using the mechanochemical method was satisfactory and similar to that observed in previous work [10,12], and by reported theoretical calculations [17], it is shown that the electron density in the excited state of BZN is shifted towards the imidazole and mainly towards the nitro group, since BZN, being an organic structure with a nitro group attached at position 2 of the imidazole, shifts the electron density towards itself. In this sense, the formation of monolayer and multilayer crystals is directly related to the coordination of the metal with the ligands and is generated in a natural way by the MOF synthesis process; multilayer crystals allow the incorporation of a greater amount of drug into the structure, in addition to providing protection to avoid its uctuation in concentration when it is in the bloodstream and tissues [18,19].…”

From Benznidazole to New Drugs: Nanotechnology Contribution in Chagas Disease

“…The inhibition in parasite growth in the presence of MOFs-EP was comparable to that observed in the culture of parasites that interacted with NFX. In the end, it was observed that the use of MOFs-EP has an inhibitory effect on circulating forms of T. cruzi similar to that observed previously with ergosterol peroxide [113], but at much lower doses of the compound and is not toxic to mammalian cells [112].…”

Recent advances and potential applications for metal-organic framework (MOFs) and MOFs-derived materials: Characterizations and antimicrobial activities

“… Compositions Linkers Antiparasitic agents Parasitic References Fe 3 O(OH)(H 2 O) 2 (BDC) 3] n (MIL-101(Fe)) H 2 BDC Dinotefuran carboxymethyl chitosan (DNF CMCS) matrix (Fam. Fulgoroidea) Planthopper [ 174 ] [Fe 3 O(OH)(H 2 O) 2 (BDCNH 2 ) 3] n (NH 2 − MIL-101(Fe)) H 2 BDCNH 2 Curcumin curc Toxoplasma gondii [ 175 ] [Zn (OAc)2(bipy)] n bipy Ergosterol peroxide EP Trypanosoma cruzi [ 176 ] [Zn 8 O(Ad) 4 (BPDC) 6 (NH2(CH 3 ) 2 ) 2] n HAd H 2 BPDC Art Fe 3 O 4 matrix Leishmania major [ 177 ] [Zr6(O)4(OH)4(BDCNH2) 6 ] n H2BDCNH 2 curc Toxoplasma gondii [ 175 ] [Ni(meim) 2]n Hmeim – mosquito larvae Aedes aegypti [ 178 ] Fe 3 O(H 2 O) 2 OH(BTC) 2] n (Fe-MIL-100) H3BTC-FIT H3BTC Azox P. infestans F. graminearum [ 179 ] (Ti 8 O 8 (OH) 4 (BDCNH 2 ) 6 ]n (MIL-125) H2BDCNH2 C. pipiens Mosquitoes [ 155 ] [Zn (OAc) 2 (bipy)] n [bipy EP EP Ergostero...…”