Comparative Analysis of Leishmania major Nucleoside Hydrolases Toward Selecting Multi-target Strategy.

PURPOSE: Leishmania causes multiple types of leishmaniasis in different parts of the world. It has a lack of metabolic machine to produce purine bases. Therefore, the parasite produces purine bases through the breakdown of nutritional nucleotides and it makes the nucleoside hydrolases (NHs) good drug targets. They have different substrate-preferring (SP) types. Our objectives were modeling and comparative analysis of these protein structures for Leishmania major. METHOD: In this work, available sequences for all SP types of L. major NH enzymes including inosine-uridine preferring NH (IUNH), inosine-guanosine preferring NH (IGNH), and inosine-adenosine-guanosine preferring NH (IAGNH) were used to make 24 structural models via SWISS-MODEL and LOMETS. After evaluating the structural models, three enzyme structures were finalized and used to analyze substrate-binding pockets. RESULTS: The three SP types of L. major NH enzymes that can breakdown purine nucleosides were highly different in terms of sequence, structure, and profile of interacting residues within the substrate-binding pockets. In this study, new enzyme structures have been presented for three SP types and they have been compared in different aspects and it indicated that they were very different from each other. CONCLUSION: Although, previously indicated that from these three SP types in genera other than Leishmania, the role of IGNH and IAGNH was greater than IUNH in supplying purine bases, till this work, just IUNH has been structurally studied and used in drug-design investigations for Leishmania. Therefore, we are offering to use all three SP types of NHs as multi-target strategy in anti-leishmaniosis drug-design studies.

A novel way for detection of antiparkinsonism drug entacapone via electrodeposition of silver nanoparticles/functionalized multi-walled carbon nanotubes as an amperometric sensor.

Silver (Ag) nanoparticles were electrochemically deposited on the film of a metformin functionalized multi-walled carbon nanotube modified glassy carbon electrode (Met-MWCNT/GCE), which fabricated an Ag@Met-MWCNT nanocomposite sensor (Ag@Met-MWCNT/GCE) to detect entacapone (ENT). The Ag@Met-MWCNT nanocomposite was characterized by field emission scanning electrochemical microscopy (FESEM), X-ray diffraction (XRD) analysis, FT-IR and electrochemical tests. The modified electrode showed a large electrocatalytic activity for reduction of ENT. This improved activity indicates that Met@MWCNT plays a crucial role in the dispersion and stabilization of Ag nanoparticles on GCE. Under the optimized conditions the linear range for the detection of the ENT was obtained to be 0.05 to 70.0µM with a low detection limit of 15.3nM. The proposed sensor can effectively analyse ENT concentration in pharmaceutical formulations and human urine samples, avoiding interference, and is a promising ENT sensor due to good sensitivity, stability and low cost.