Molecular Mechanism Underlying Hesperetin-induced Apoptosis by in silico Analysis and in Prostate Cancer PC-3 Cells Docking;hesperetin;apoptosis;NF-${\kappa}B$; Aim: To investigate the molecular mechanisms underlying triggering of apoptosis by hesperetin using in silico and in vitro methods. Methods: The mechanism of binding of hesperetin with NF-${\kappa}B$ and other apoptotic proteins like BAX, BAD, $BCL_2$ and $BCL_{XL}$ was analysed in silico using Schrodinger suite 2009. In vitro studies were also carried out to evaluate the potency of hesperetin in inducing apoptosis using the human prostate cancer PC-3 cell line. Results: Hesperetin was found to exhibit high-affinity binding resulting from greater intermolecular forces between the ligand and its receptor NF-${\kappa}B$ (-7.48 Glide score). In vitro analysis using MTT assay confirmed that hesperetin reduced cell proliferation ($IC_{50}$ values of 90 and $40{\mu}M$ at 24 and 48h respectively) in PC-3 cells. Hesperetin also downregulated expression of the anti-apoptotic gene $BCL_{XL}$ at both mRNA and protein levels and increased the expression of pro-apoptotic genes like BAD at mRNA level and BAX at mRNA as well as protein levels. Conclusion: The results suggest that hesperetin can induce apoptosis by inhibiting NF-${\kappa}B$.

Edwardsiella tarda and Flavobacterium columnare are two important intracellular pathogenic bacteria that cause the infectious diseases edwardsiellosis and columnaris in wild and cultured fish. Prediction of major histocompatibility complex (MHC) binding is an important issue in T-cell epitope prediction. In a healthy immune system, the T-cells must recognize epitopes and induce the immune response. In this study, T-cell epitopes were predicted by using in silico immunoinformatics approach with the help of bioinformatics tools that are less expensive and are not time consuming. Such identification of binding interaction between peptides and MHC alleles aids in the discovery of new peptide vaccines. We have reported the potential peptides chosen from the outer membrane proteins (OMPs) of E. tarda and F. columnare, which interact well with MHC class I alleles. OMPs from E. tarda and F. columnare were selected and analyzed based on their antigenic and immunogenic properties. The OMPs of the genes TolC and FCOL_04620, respectively, from E. tarda and F. columnare were taken for study. Finally, two epitopes from the OMP of E. tarda exhibited excellent protein–peptide interaction when docked with MHC class I alleles. Five epitopes from the OMP of F. columnare had good protein–peptide interaction when docked with MHC class I alleles. Further in vitro studies can aid in the development of potential peptide vaccines using the predicted peptides.

In Silico Docking Studies of Selected Flavonoids - Natural Healing Agents against Breast Cancer Breast cancer;flavonoids;human estrogen receptor;argus lab;docking; Background: Breast cancer is the serious health concern in India causing the highest mortality rate in females, which occurs due to uncontrolled cell division and can be metastasize to other parts of the human body. Interactions with estrogen receptor (ER) alpha are mainly responsible for the malignant tumors with regulation of the transcription of various genes as a transcription factor. Most of the drugs currently used for the breast cancer treatment produce various side effects and hence we focused on natural compounds which do not exhibit any toxic effect against normal human cells. Materials and Methods: Structure of human ER was retrieved from the Protein Data Bank and the structures of flavonoid compounds have been collected from PubChem database. Molecular docking and drug likeness studies were performed for those natural compounds to evaluate and analyze the anti-breast cancer activity. Results: Finally two compounds satisfying the Lipinski's rule of five were reported. The two compounds also exhibited highest binding affinity with human ER greater than 10.5 Kcal/mol. Conclusions: The results of this study can be implemented in the drug designing pipeline.

The third leading cause of death in the world is Diabetes. Diabetes comes under a group of metabolic disorders in which the patients possess high blood glucose level. Camptothecin is an alkaloid compound with better antioxidant activity and in china it was used as traditional drugs to cure many diseases. The early researches on camptothecin revealed that it possess better anticancer and antitumor activity when compared with current available synthetic drugs. In silico drug designing and docking studies pave a way for better understanding of inhibitory activity of the compound over the respective target proteins. Molecular docking is one of the most powerful tools for predicting and analyzing the binding interactions between receptors and small molecules at the atomic level. In the current study, an in silico binding interaction of the compound camptothecin with three important diabetic targets like Glucokinase, insulin receptor and PPAR gamma were analyzed using Arguslab. ArgusLab software is used for molecular docking, to study the interactions between small compounds and its proteins. The compound camptothecin was first tested for its drug likeliness, bioactive properties and the results predicted that the compound passed the test for being an oral drug. The docking study revealed that camptothecin showed best binding affinity towards all the three proteins. Among the three proteins, PPAR gamma protein exhibited the lowest binding energy, followed by Glucokinase and insulin receptor with the binding energy of >-8.5 kcal/mol. Thus, Camptothecin compound could be considered as a better lead molecule in the development and discovery of new anti-diabetic drugs.