Homology Modelling, Molecular Docking and Molecular Dynamics Simulation Studies of CALMH1 against Secondary Metabolites of Bauhinia variegata to Treat Alzheimer's Disease.

Calcium homeostasis modulator 1 (CALHM1) is a protein responsible for causing Alzheimer's disease. In the absence of an experimentally designed protein molecule, homology modelling was performed. Through homology modelling, different CALHM1 models were generated and validated through Rampage. To carry out further in silico studies, through molecular docking and molecular dynamics simulation experiments, various flavonoids and alkaloids from Bauhinia variegata were utilised as inhibitors to target the protein (CALHM1). The sequence of CALHM1 was retrieved from UniProt and the secondary structure prediction of CALHM1 was done through CFSSP, GOR4, and SOPMA methods. The structure was identified through LOMETS, MUSTER, and MODELLER and finally, the structures were validated through Rampage. Bauhinia variegata plant was used to check the interaction of alkaloids and flavonoids against CALHM1. The protein and protein-ligand complex were also validated through molecular dynamics simulations studies. The model generated through MODELLER software with 6VAM A was used because this model predicted the best results in the Ramachandran plot. Further molecular docking was performed, quercetin was found to be the most appropriate candidate for the protein molecule with the minimum binding energy of -12.45 kcal/mol and their ADME properties were analysed through Molsoft and Molinspiration. Molecular dynamics simulations showed that CALHM1 and CALHM1-quercetin complex became stable at 2500 ps. It may be seen through the study that quercetin may act as a good inhibitor for treatment. With the help of an in silico study, it was easier to analyse the 3D structure of the protein, which may be scrutinized for the best-predicted model. Quercetin may work as a good inhibitor for treating Alzheimer's disease, according to in silico research using molecular docking and molecular dynamics simulations, and future in vitro and in vivo analysis may confirm its effectiveness.

Screening and identification of secondary metabolites in the bark of Bauhinia variegata to treat Alzheimer's disease by using molecular docking and molecular dynamics simulations.

Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) acts as a promising protein targets for which drug as an inhibitor can be designed to treat Alzheimer's Disease. Different flavonoids and alkaloids of Bauhinia variegata were used as an inhibitor to target the protein. The current in silico study was carried out to explore the binding patterns of flavanoids and alkaloids against Acetylcholinesterase (PDB ID: 4PQE) and Butyrylcholinesterase (PDB ID: 1P0I) using molecular docking and molecular dynamics simulations approach. Molecular docking result shows that Dihydroquercetin (CID:439533) binds with the active region of AChE and BChE. Using molsoft, molinspiration, and pkCSM all the properties of the candidate were analyzed. The best compound Dihydroquercetin was compared with Donepezil drug through molecular dynamic simulation studies. The analysis of Molecular Dynamics Simulations showed that AChE and AChE-Dihydroquercetin complex became stable at 3000 ps and there was little conformational change in BChE and BChE-Dihydroquercetin complex. The in silico study finally predicts that Dihydroquercetin may act as a good inhibitor for treating Alzheimer's disease and further in vitro and in vivo studies may prove its therapeutic potential.Communicated by Ramaswamy H. Sarma.

Stevioside mediated chemosensitization studies and cytotoxicity assay on breast cancer cell lines MDA-MB-231 and SKBR3.

Cancer is one of the most impacting life-threatening disease for the human populace. Hence, over the years we have seen a consistent interest to study and investigate new treatments to cure and prevent this disease. Medicinal plants have played a progressive part in treatment since many years. In this research study, we have explored the cytotoxicity effect of purified bioactive compound isolated from Stevia rebaudiana leaves and the key mechanism responsible for apoptosis in human breast cancer cells. The anticancer properties of Stevia rebaudiana leaves has been suggested in earlier literature. Hence, the aim of this study was to investigate the cytotoxicity of purified stevioside in human breast cancer cell lines MDA-MB-231 and SKBR3. Results showed that purified stevioside inhibited the growth of cancerous cell lines. The IC50 obtained after treatment with stevioside on cancer cells MDA-MB-231 and SKBR3 are 55 µM and 66 µM respectively. This shows purified stevioside is capable of inducing apoptosis indicating its promising anticancer activity. However, so far chemosensitization effects of stevioside on breast cancer have not been fully explained by other studies. Hence, additionally, this study also evaluates the chemosensitization potential of stevioside in combination with 5-FU. This research study shows the importance of Stevia rebaudiana as a good source of bioactive compounds with high anti-cancer property.