Iron oxide nanoparticles (INPs) have potential biological, biomedical and environmental applications. These applications require surface modification of the iron oxide nanoparticles, which makes it non-toxic, biocompatible, stable and non-agglomerative in natural and biological surroundings. In the present study, iron oxide nanoparticles (INPs) and chitosan oligosaccharide coated iron oxide nanoparticles (CSO-INPs) were synthesized to evaluate the effect of surface coating on the stability and toxicity of nanoparticles. Comparative in vitro cytotoxicity of nanoparticles was evaluated in HeLa (human cervix carcinoma), A549 (human lung carcinoma) and Hek293 (human embryonic kidney) cells by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay along with flow cytometry study for cell viability, membrane integrity, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) production. Morphological alteration in nanoparticles treated cells was analyzed by Acridine orange/ethidium bromide double staining and electron microscopy. Synthesized nanoparticles were found to be spherical in shape, well dispersed and stable at various pH values, making them suitable for biomedical and environmental applications. The present study also indicates that the chitosan oligosaccharide coating on iron oxide nanoparticles results in the decrease in cellular damage and moderate ROS production, thereby, significantly decreasing the cytotoxic impact of bare iron oxide nanoparticles.
Protein phosphorylation is an important mechanism that implicates in physiology of any organism including parasitic protozoa. Metallic protein Ser/Thr protein phosphatase 5 (PP5) controls various cellular signaling pathways of Plasmodium falciparum. The structure and inhibitory mechanism of PP5 in P. falciparum is not known. In fact, no experimental structural data are available for P. falciparum Ser/Thr protein phosphatase 5 (PfPP5) till date. Hence, we have proposed computer-generated model of catalytic subunit of PfPP5 and its inhibitory mechanism was analyzed. A set of 42 known natural inhibitors of protein phosphate family were docked against metal-binding catalytic site of PfPP5 and we found that cantharidin and its derivatives shows better binding energy among them. Similarity search was performed by taking these compounds as lead compounds against PubChem and ChemBank. The search result provides 3703 similar compounds; out of which 2245 qualified the Lipinski rule of five. Further, virtual screening of these compounds was performed and selected top 25 were selected on the basis of binding energy. In continuation, rigid and flexible docking of these screened compounds was performed to get the insight of interactions. Finally, top 5 compounds were verified for ADMET properties, and then, all are subjected to MD simulations for 25 ns in order to validate their stability. Compounds CBI: 3554182, CID: 23561913, and CID: 21168680 showed most stable binding, although some of hydrogen bonds pairing varied throughout simulation. These finding would be helpful to the medicinal chemists for the development of antimalarial drugs to combat this deadly disease.
Amebiasis, a major health problem in developing countries, is the second most common cause of death due to parasitic infection. Amebiasis is usually transmitted by the ingestion of
Entamoeba histolytica
cysts through oral–fecal route. Herein, we report on the use of chitosan oligosaccharide-functionalized iron oxide nanoparticles for efficient capture and removal of pathogenic protozoan cysts under the influence of an external magnetic field. These nanoparticles were synthesized through a chemical synthesis process. The synthesized particles were characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and zeta potential analysis. The particles were found to be well dispersed and uniform in size. The capture and removal of pathogenic cysts were demonstrated by fluorescent microscopy, transmission electron microscopy, and scanning electron microscopy (SEM). Three-dimensional modeling of various biochemical components of cyst walls, and thereafter, flexible docking studies demonstrate the probable interaction mechanism of nanoparticles with various components of
E. histolytica
cyst walls. Results of the present study suggest that
E. histolytica
cysts can be efficiently captured and removed from contaminated aqueous systems through the application of synthesized nanoparticles.
Tuberculosis, a pandemic disease is caused by Mycobacterium tuberculosis (Mtb). DNA polymerase III encoded by DnaE2 of Mtb is specifically required for its survival in vivo, and hence can be considered to be a potential drug target. Amino acid sequence analysis of the MtbDnaE2 and its human counterpart does not show any significant similarity. Therefore, a 3D model of the MtbDnaE2 was generated using Modeller 9v10 with the template structure of E. Coli DNA polymerase III alpha subunit (2HNH_A). The generated models were validated using a number of programmes such as RAMPAGE/PROCHECK, VERIFY_3D, and ProSA. MtbDnaE2 has few conserved residues and four conserved domains similar to that present in DNA polymerase III of E. coli. In silico screening was performed with bioactive anti-tuberculosis compounds and 6-AU (a known inhibitor of DNA polymerase III of Bacillus subtilis) and its analogues against the modeled MtbDnaE2 structure. Docking was performed using GOLD v5.2 software which resulted in the identification of top ten compounds with high GOLD fitness scores and binding affinity (X-Score). To further evaluate the efficacy of these compounds, in silico ADMET analysis was performed using MedChem Designer v3. Given their high binding affinity to the targeted MtbDnaE2, which is essential for DNA replication in the Mtb and good ADMET properties, these compounds are promising candidates for further evaluation and development as anti-tubercular agents.
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