Background: Alzheimer’s Disease (AD) has become the most common age-dependent disease of dementia. The trademark pathologies of AD are the presence of amyloid aggregates in neurofibrils. Recently phytochemicals being considered as potential inhibitors against various neurodegenerative, antifungal, antibacterial and antiviral diseases in human beings. Objective: This study targets the inhibition of BACE-1 by phytochemicals using in silico drug discovery analysis. Methods: A total of 3150 phytochemicals were collected from almost 25 different plants through literature assessment. The ADMET studies, molecular docking and density functional theory (DFT) based analysis were performed to analyze the potential inhibitory properties of these phytochemicals. Results: The ADMET and docking results exposed seven compounds that have high potential as an inhibitory agent against BACE-1 and show binding affinity >8.0 kcal/mol against BACE-1. They show binding affinity greater than those of various previously reported inhibitors of BACE-1. Furthermore, DFT based analysis has shown high reactivity for these seven phytochemicals in the binding pocket of BACE- 1, based on ELUMO, EHOMO and Kohn-Sham energy gap. All seven phytochemicals were testified (as compared to experimental ones) as novel inhibitors against BACE-1. Conclusion: Out of seven phytochemicals, four were obtained from plant Glycyrrhiza glabra i.e. Shinflavanone, Glabrolide, Glabrol and PrenyllicoflavoneA, one from Huperzia serrate i.e. Macleanine, one from Uncaria rhynchophylla i.e. 3a-dihydro-cadambine and another one was from VolvalerelactoneB from plant Valeriana-officinalis. It is concluded that these phytochemicals are suitable candidates for drug/inhibitor against BACE-1, and can be administered to humans after experimental validation through in vitro and in vivo trials.

Objectives: Type-2 diabetes mellitus, caused by impaired secretion of insulin, is becoming one of the health hazardous threats to human lives across the world. Its prevalence is rising with time. In this study, 2750 phytochemicals, that are considered to have great ability to eliminate diseases caused by different viruses and bacteria, are obtained from different medicinal plants and discovery of inhibitors through in silico method was performed against Dipeptidyl peptidase-4 (DPP4). Method: The pharmacological assessment and pharmacokinetics of phytochemicals, molecular docking and density functional theory (DFT) analysis helped to explore the inhibitory action of phytochemicals against DPP4. Total forty-nine phytochemicals were screened initially to reduce the number of compounds to be analyzed further based on a threshold of binding affinity ≥-5.5 kcal/mol and were considered for further computational studies to analyze their inhibitory effects for DPP4. For comparison and validation of the results of present study, various previously reported and experimentally validated compounds were docked with the DPP4. For these dockings, binding affinity was predicted and compared with those of phytochemicals to check if these phytochemicals are competent enough to be used as an inhibitor in the treatment of diabetes mellitus in the future. Results: Only four phytochemicals showed binding affinity greater than those of experimentally validated compounds. These included two phytochemicals from Silybum marianum, i.e. Diprenyleriodictyol and Taxifolin and while other two phytochemicals from Santolina insularis and Erythrina Varigatae i.e. Papraline and Osajin respectively. The reactivity levels for these four phytochemicals with the binding site residues of DPP4 were obtained by DFT based analysis, in which ELUMO, EHOMO and band energy gap were computed. Conclusion: Based on these results, it is concluded that these four phytochemicals, after passing through in vitro and in vivo validation, can be utilized as potential DPP4 inhibitors as they have strong properties as compared to those of various experimentally validated inhibitors. with about 300 million cases is to be expected worldwide by 2025 [3]. Both genetic and environmental factors are involved in pathogenicity of type-2 diabetes. It may result in many other disorders like obesity, increased thirst, frequent urination and physical inactivity [4]. There are many symptoms of type-2 diabetes but one of the main symptoms is of raising the blood glucose levels, which is usually caused by impaired In silico discovery of potential inhibitors against Dipeptidyl Peptidase-4: A major biological target of Type-2 diabetes mellitus

Parkinson's disease, caused by mutations in the Parkin that leads to loss of neuron is the second most widespread neurodegenerative disorder in the world. Phytochemicals are being considered due to their medicinal properties to cure many human diseases. The present study targets the inhibition of Parkin, a major biological target for Parkinson using 3150 phytochemicals from various medicinal plants. These plants are naturally growing in a local climate of Pakistan, India and China and being used for a long time for the medicinal purpose. A total of 3150 phytochemicals from various medicinal plants were collected for this in silico study. The pharmacological assessments prediction, molecular docking and density functional theory (DFT) based studies were done to fi nd out the latent inhibitory properties of these phytochemicals against Parkin. Out of 3150 phytochemicals, 175 showed human-suitable pharmacological properties and among those 175 compounds, 5 phytochemicals, i.e. Liquirtin, Shinfl avanone, Glabrone, GlycyrdioneB and IsoangustoneA to have potent inhibitory properties against Parkin and can be deliberated for additional in vitro and in vivo studies to evaluate their inhibitory eff ects against Parkin. They revealed binding affi nity greater than various previously reported inhibitors against Parkin. Additionally, DFT based analysis exhibited high reactivity for these fi ve phytochemicals in the binding pocket of Parkin, based on E LUMO , E HOMO and band energy gap. A total of 5 out of 175 phytochemicals are reported as highly potent inhibitors against Parkin which are liquirtin, Shinfl avanone, Glabrone, Glycyrdione B and IsoangustoneA from the same medicinal plant Glycyrrhiza glabra. However, these 5 phytochemicals can be considered for further in vivo and in vitro analysis for the clinical development of a drug against the world's second most common brain disorder, the Parkinson's disease.