Novel Fused Pyrimidines as Potent Cyclin-Dependent Kinases Inhibitor for Gastric Adenocarcinoma: Combined In Vitro, In Silico Anticancer Studies.

Our research aims to design novel pyrimidine derivatives inspired by the common pyrimidine core found in many FDA-approved drugs. However, extensive prior research on the pyrimidine scaffold has made discovering new molecules more challenging. To overcome this obstacle, we employed a molecular hybridisation strategy, opting to hybridise tetralin and pyrimidine, recognising their potential in cancer therapeutics.

Machine learning models to identify lead compound and substitution optimization to have derived energetics and conformational stability through docking and MD simulations for sphingosine kinase 1.

Sphingosine kinases (SphKs) are a group of important enzymes that circulate at low micromolar concentrations in mammals and have received considerable attention due to the roles they play in a broad array of biological processes including apoptosis, mutagenesis, lymphocyte migration, radio- and chemo-sensitization, and angiogenesis. In the present study, we constructed three classification models by four machine learning (ML) algorithms including naive bayes (NB), support vector machine (SVM), logistic regression, and random forest from 395 compounds. The generated ML models were validated by fivefold cross validation.

Identification of potential marine bioactive compounds from brown seaweeds towards BACE1 inhibitors: molecular docking and molecular dynamics simulations approach.

Unlabelled: The drug target protein β-secretase 1 (BACE1) is one of the promising targets in the design of the drugs to control Alzheimer's disease (AD). Patients with neurodegenerative diseases are increasing in number globally due to the increase in the average lifetime. Neuro modulation is the only remedy for overcoming these age related diseases.

Identification of a novel drug molecule for neurodegenerative disease from marine algae through analysis.

Cognitive functions are lost due to the rapid hydrolysis of acetylcholine including Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE). Marine algae-derived compounds were reported for their neuroprotective activities and hence they can be utilised for treating neurodegenerative ailments like Alzheimer's Disease and Parkinson's Disease which are due to the loss of cognitive functions. Major attention is currently paid to seaweeds due to their health benefits and high nutritional values.

Discovery of potential TAAR1 agonist targeting neurological and psychiatric disorders: An in silico approach.

Trace amine-associated receptor 1 (TAAR1) is a G-protein-coupled receptor which is primarily expressed in the brain. It is activated by trace amines which play a role in regulating neurotransmitters like dopamine, serotonin and norepinephrine. TAAR1 agonists have potential applications in the treatment of neurological and psychiatric disorders, especially schizophrenia.

Orphan receptor GPR88 as a potential therapeutic target for CNS disorders - an approach.

The G-protein-coupled receptors are a part of the largest and most physiologically relevant family of membrane proteins. One-third of the medications, now on the market, target the GPCR receptor family, which is one of the most important therapeutic targets for many disorders. In the reported work, we have focussed on orphan GPR88 receptor which is a part of the GPCR protein family and a potential target for central nervous system disorders.

Evaluation of action of steroid molecules on SARS-CoV-2 by inhibiting NSP-15, an endoribonuclease.

Many countries in the world have recently experienced an outbreak of COVID-19, turned out to be a pandemic which significantly affected the world economy. Among many attempts to treat/control infection or to modulate host immunity, many small molecules including steroids were prescribed based on their use against other viral infection or inflammatory conditions. A recent report established the possibility of usage of a corticosteroid against the virus through inhibiting NSP-15; an mRNA endonuclease of SARS-CoV-2 and thereby viral replication.

Structure-based pharmacophore modeling, virtual screening approaches to identifying the potent hepatitis C viral protease and polymerase novel inhibitors.

Hepatitis C is an infectious disease that leads to acute and chronic liver illnesses. Currently, there are no effective vaccines against this deadly virus. Direct acting antiviral (DAA) drugs are given in the combination with ribavirin and pegylated interferon which lead to adverse effects.

Identification of a Chlorogenic Ester as a Monoamine Oxidase (MAO-B) Inhibitor by Integrating "Traditional and Machine Learning" Virtual Screening and In Vitro as well as In Vivo Validation: A Lead against Neurodegenerative Disorders?

Parkinson's disease (PD) is the furthermost motor disorder of adult-onset dementia connected to memory and other cognitive abilities. Monoamine oxidases (MAOs) have gained significant attention in recent years owing to their possible therapeutic use against PD. Expression of MAO-B has been found to be elevated in PD patients for increased uptake of dopamine, producing hydrogen peroxide and finally causing neuronal injury.

Piperazine-substituted derivatives of favipiravir for Nipah virus inhibition: What do in silico studies unravel?

Unlabelled: Favipiravir is found to show excellent in-vitro inhibition activity against Nipah virus. To explore the structure-property relationship of Favipiravir, in silico designing of a series of piperazine substituted Favipiravir derivatives are attempted and computational screening has been done to evaluate its bimolecular interactions with Nipah virus. The geometrical features of all the molecules have been addressed from Density Functional Theory calculations.

N-substitution in isatin thiosemicarbazones decides nuclearity of Cu(II) complexes - Spectroscopic, molecular docking and cytotoxic studies.

The mono- (1) and bi-nuclear (2) copper(II) complexes containing N-substituted isatin thiosemicarbazone(s) were synthesized, and characterized by analytical and spectroscopic (UV-Visible, FT-IR and EPR) techniques. Bimetallic nature of complex 2 was confirmed by single crystal X-ray crystallography. The structures predicted by spectroscopic and crystallographic methods were validated by computational studies.

Screening of potential drug for Alzheimer's disease: a computational study with GSK-3 β inhibition through virtual screening, docking, and molecular dynamics simulation.

The global impact of Alzheimer's disease (AD) necessitates intensive research to find appropriate and effective drugs. Many studies in AD suggested beta-amyloid plaques and neurofibrillary tangles-associated tau protein as the key targets for drug development. On the other hand, it is proved that triggering of Glycogen Synthase Kinase-3β (GSK-3β) also cause AD, therefore, GSK-3β is a potential drug target to combat AD.

Fucoidan serves a neuroprotective effect in an Alzheimer's disease model.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that causes memory and cognitive deficits. The present study was carried out to evaluate the protective effects of fucoidan in monocrotophos induced AD in Drosophila melanogaster. In silico studies showed that fucoidan exhibited binding energy of -9.

Identification of novel NAD(P)H dehydrogenase [quinone] 1 antagonist using computational approaches.

NAD(P)H: quinone oxidoreductase 1 (NQO1) inhibitors are proved as promising therapeutic agents against cancer. This study is to determine potent NAD(P)H-dependent NQO1 inhibitors with new scaffold. Pharmacophore-based three-dimensional (3D) QSAR model has been built based on 45 NQO1 inhibitors reported in the literature.

Identification of potential PKC inhibitors through pharmacophore designing, 3D-QSAR and molecular dynamics simulations targeting Alzheimer's disease.

Protein kinases are ubiquitously expressed as Serine/Threonine kinases, and play a crucial role in cellular activities. Protein kinases have evolved through stringent regulation mechanisms. Protein kinases are also involved in tauopathy, thus are important targets for developing Anti-Alzheimer's disease compounds.

Identification of new BACE1 inhibitors using Pharmacophore and Molecular dynamics simulations approach.

Inhibition of β-Secretase (BACE1) is crucial for the treatment of Alzheimer's disease (AD). Availability of BACE1 crystal structures in both apo and complexed forms enables to find structure-based BACE1 inhibitors for controlling AD. There are two catalytic aspartates (ASP32 and ASP228) presents in the active domain of BACE1.

Synthesis, structural elucidation, antioxidant, CT-DNA binding and molecular docking studies of novel chloroquinoline derivatives: Promising antioxidant and anti-diabetic agents.

The synthesized novel chloroquinoline derivatives 1-(2-chloro-4-phenylquinolin-3-yl)ethanone (CPQE), 1-(2,6-dichloro-4-phenylquinolin-3-yl)ethanone (DCPQE), methyl 2,6-dichloro-4-phenylquinoline-3-carboxylate (MDCPQC),methyl 2-chloro-4-methylquinoline-3-carboxylate (MCMQC) were subjected to the elementary analysis like FT-IR, NMR and Mass spectra using GCMS. Also, single crystal X-ray diffraction study was executed for the compound MDCPQC. The crystal packing is stabilized by C-H…π and π-π interactions and also Chlorine-Chlorine short intermolecular contacts generating a three-dimensional supramolecular network.

Identification of type I and type II inhibitors of c-Yes kinase using in silico and experimental techniques.

c-Yes kinase is considered as one of the attractive targets for anti-cancer drug design. The DFG (Asp-Phe-Gly) motif present in most of the kinases will adopt active and inactive conformations, known as DFG-in and DFG-out and their inhibitors are classified into type I and type II, respectively. In the present study, two screening protocols were followed for identification of c-Yes kinase inhibitors.