Promising Novel Anti-parasitic Drug Nitazoxanide/Mn Metal Complex with its Spectroscopic Characterization, Molecular Docking, DFT Analysis and Assessment of its in vitro Antioxidant Activity

Nitazoxanide (NITA) possesses a high potential activity against infections by various protozoa, but there is an urgent need for the development of new anti-pathogens with diverse metal chelation mechanisms to mitigate any possible side effects. Novel nitazoxanide/Mn complex (NITA/Mn) was chemically synthesized and fully characterized. Recent studies on metallic complexes present promising therapeutic agents against various diseases. As Manganese (Mn) acts as a critical antioxidant by serving as the essential metal cofactor for (MnSOD), the primary enzyme responsible for scavenging superoxide radicals in mitochondria, it was the target for chelation with NITA to synthesize a new potent antioxidant to alleviate any oxidative signs produced by NITA.

(NITA/Mn) complex was characterized using C,H, N and S elemental analysis, conductivity value, IR, UV, SEM and TEM, this paper explain the effect of NITA and NITA/Mn on oxidative stress via using antioxidant assays such as “ABTS, DPPH and metal chelation” assay with estimation of the novel synthesized metal complex stability via DFT analysis, The estimated percentages obtained of the chelating activity of NITA/Mn via using different assays of scavenging free radicals. (ABTS, DPPH and metal chelation) assays. Sigma receptors Sigma α-1 receptors are unique; chaperone proteins located primarily in the endoplasmic reticulum (ER) membrane. They are expressed intracellularly in neurons and glia cells and act as the main pharmacochaperones to control neurotransmission by affecting the level of expression of different transporters and receptors. Hence, the cellular receptors of sigma are considered to be involved in the direct potential effects of a lot of drugs. Thus, simulation docking was performed between the Sigma receptor and the novel complex (NITA/Mn).

Based on the molar conductivity value, the (NITA/Mn) complex proved to have a non-electrolytic nature. NITA possess two donation sites through the nitrogen atom of O=C-NH (amide group) and oxygen atom of the O-C=O (ester group) toward Mn (II) metal ion, which was confirmed by IR and UV. SEM and TEM images showed small particles that agglomerated in different shapes. All DFT analysis reinforces that Mn-NITA is energetically more stable and less reactive. The current metal complex NITA/Mn recently chelates with the sigma receptor very effectively via high-forcing docking. The estimated potent scavenging capacities of NITA/Mn confirmed that the capacity of the NITA/Mn complex to scavenge the free radicals of ABTS, DPPH and metal chelation was higher, confirming new potent antioxidant capacities of the synthesized complex. NITA/Mn triggered promising results via a more stable synthesized formula and acted as a potent agent with antioxidant capacities.