Virtual screening of natural anti-filarial compounds against glutathione-S-transferase of Brugia malayi and Wuchereria bancrofti.

Glutathione-S-transferase also referred as GST is one of the major detoxification enzymes in parasitic helminths. The crucial role played by GST in various chronic infections has been well reported. The dependence of nematodes on detoxification enzymes to maintain their survival within the host established the crucial role of GST in filariasis and other related diseases. Hence, this well-established role of GST in filariasis along with its greater nonhomology with its human counterpart makes it an important therapeutic drug target. Here in this study, we have tried to explore the inhibitory potential of some of the well-reported natural ant-filarial compounds against the GST from Wuchereria bancrofti (W.bancrofti) and Brugia malayi (B.malayi). In silico virtual screening, approach was used to screen the selected natural compounds against GST from W.bancrofti and B.malayi. On the basis of our results, here we are reporting some of the natural compounds which were found to be very effective against GSTs. Along with we have also revealed the characteristic of the active site of BmGST and WbGST and the role of important active site residues involve in the binding of natural compounds within the active site of GSTs. This information will oped doors for using natural compounds as anti-filarial therapy and will also be helpful for future drug discovery.

Magnetic Nanoparticles: Properties, Synthesis and Biomedical Applications.

Importance of magnetic nanoparticles in daily life including biomedical applications in near future cannot be overlooked. This review focuses on the properties of magnetic nanoparticles (MNPs), various approaches for their synthesis, and their biomedical applications. First part of this review focuses on the classes, physical properties, and characteristics of MNPs. The second part sheds light on strategies developed for the synthesis of MNPs, with special attention given to biological, physical, and chemical approaches as well as recent modifications in the preparation of monodispersed samples. Furthermore, this review deals with the biomedical applications of MNPs, which includes applications in targeted drug delivery, diagnostics, gene therapy, hyperthermia and advantages in the field of medicine.

Implication of Caspase-3 as a Common Therapeutic Target for Multineurodegenerative Disorders and Its Inhibition Using Nonpeptidyl Natural Compounds.

Caspase-3 has been identified as a key mediator of neuronal apoptosis. The present study identifies caspase-3 as a common player involved in the regulation of multineurodegenerative disorders, namely, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). The protein interaction network prepared using STRING database provides a strong evidence of caspase-3 interactions with the metabolic cascade of the said multineurodegenerative disorders, thus characterizing it as a potential therapeutic target for multiple neurodegenerative disorders. In silico molecular docking of selected nonpeptidyl natural compounds against caspase-3 exposed potent leads against this common therapeutic target. Rosmarinic acid and curcumin proved to be the most promising ligands (leads) mimicking the inhibitory action of peptidyl inhibitors with the highest Gold fitness scores 57.38 and 53.51, respectively. These results were in close agreement with the fitness score predicted using X-score, a consensus based scoring function to calculate the binding affinity. Nonpeptidyl inhibitors of caspase-3 identified in the present study expeditiously mimic the inhibitory action of the previously identified peptidyl inhibitors. Since, nonpeptidyl inhibitors are preferred drug candidates, hence, discovery of natural compounds as nonpeptidyl inhibitors is a significant transition towards feasible drug development for neurodegenerative disorders.

Antioxidant and α -amylase inhibitory property of phyllanthus virgatus L.: an in vitro and molecular interaction study.

The present study on Phyllanthus virgatus, known traditionally for its remedial potential, for the first time provides descriptions of the antioxidant and inhibition of α -amylase enzyme activity first by in vitro analyses, followed by a confirmatory in silico study to create a stronger biochemical rationale. Our results illustrated that P. virgatus methanol extract exhibited strong antioxidant and oxidative DNA damage protective activity than other extracts, which was well correlated with its total phenolic content. In addition, P. virgatus methanol extract strongly inhibited the α -amylase activity (IC50 33.20 ± 0.556 µ g/mL), in a noncompetitive manner, than acarbose (IC50 76.88 ± 0.277 µ g/mL), which showed competitive inhibition. Moreover, this extract stimulated the glucose uptake activity in 3T3-L1 cells and also showed a good correlation between antioxidant and α -amylase activities. The molecular docking studies of the major bioactive compounds (9,12-octadecadienoic acid, asarone, 11-octadecenoic acid, and acrylic acid) revealed via GC-MS analysis from this extract mechanistically suggested that the inhibitory property may be due to the synergistic effect of these bioactive compounds. These results provide substantial basis for the future use of P. virgatus methanol extract and its bioactive compound in in vivo system for the treatment and management of diabetes as well as in the related condition of oxidative stress.