Identification of potential death-associated protein kinase-1 (DAPK1) inhibitors by an integrated ligand-based and structure-based computational drug design approach.

Death-associated protein kinase 1 (DAPK1) is a calcium/calmodulin (Ca/CaM)-dependent serine/threonine kinase that is abundantly expressed in the memory- and cognition-related brain areas. DAPK1 is associated with several pathological hallmarks of Alzheimer's disease (AD); it is an attractive target for designing a novel DAPK1 inhibitor as an effective therapeutic treatment for AD. In the present study, we have used an integrated ligand-based and structure-based drug design method to identify DAPK1 inhibitors.

Combined ligand-based and structure-based design of PDE 9A inhibitors against Alzheimer's disease.

PDE9 enzyme hydrolyzes cGMP, which is involved in the regulation of synaptic plasticity through the NMDA pathway (a well-known excitotoxic target for AD) via activation of calcium/calmodulin-dependent neuronal NO synthases in the postsynaptic neurons. The inhibition of PDE9 leads to elevated cGMP levels, causing enhanced NMDA signaling and thus contributing to an increase in synaptic plasticity and stabilization. Therefore, it could be considered a pertinent target for AD drug discovery.

Pharmacophore-based virtual screening, molecular docking and molecular dynamics simulations study for the identification of LIM kinase-1 inhibitors.

LIM kinases (LIMKs) are a family of protein kinases involved in the regulation of actin dynamics. There are two isoforms of LIMKs i.e.

Cathepsin B-A Neuronal Death Mediator in Alzheimer's Disease Leading to Neurodegeneration.

The lysosomal cysteine protease enzyme, named Cathepsin B, mainly degrades the protein and manages its average turnover in our body. The Cathepsin B active form is mostly present inside the lysosomal part at a cellular level, providing the slightly acidic medium for its activation. Multiple findings on Cathepsin B reveal its involvement in neurons' degeneration and a possible role as a neuronal death mediator in several neurodegenerative diseases.

Identification of sulfonamide based butyrylcholinesterase inhibitors through scaffold hopping approach.

Butyrylcholinesterase (BChE), a hydrolytic enzyme, is responsible for the termination of the action of acetylcholine besides acetylcholinesterase (AChE) in the synaptic cleft of the brain. The alteration in the enzyme level, in patients with the progression of Alzheimer's disease, makes it a therapeutic target. In the present study, we developed BChE inhibitors through scaffold hopping by exploring two previously reported compounds, i.

Systematic review on role of structure based drug design (SBDD) in the identification of anti-viral leads against SARS-Cov-2.

The outbreak of existing public health distress is threatening the entire world with emergence and rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The novel coronavirus disease 2019 (COVID-19) is mild in most people. However, in some elderly people with co-morbid conditions, it may progress to pneumonia, acute respiratory distress syndrome (ARDS) and multi organ dysfunction leading to death.

A systematic review of carbohydrate-based bioactive molecules for Alzheimer's disease.

The abundance, low cost, high density of functional groups and ease of purification of carbohydrates are among the most important features that make them a prime candidate for designing therapeutics. Several carbohydrate-based molecules, of both natural and synthetic origin, are known for their wide range of therapeutic activities. The incorporation of a carbohydrate moiety not only retains the pharmacological characteristics of a molecule but also improves its activity.

Multifunctional hybrid sulfonamides as novel therapeutic agents for Alzheimer's disease.

A breakthrough in modern medicine, in terms of treatment of Alzheimer's disease, is yet to be seen, as the scene is currently plagued with numerous clinical trial failures. Here, we are exploring multifunctional hybrid sulfonamides for their anti-Alzheimer activity due to the complex nature of the disease. Compound 41 showed significant inhibition of MMP-2 (IC: 18.

Rational approaches of drug design for the development of selective estrogen receptor modulators (SERMs), implicated in breast cancer.

Drug discovery and development have gained momentum due to the rational drug design by engaging computational tools and bioinformatics methodologies. Bioisosteric replacements and hybrid molecular approaches are the other inventive processes, used by medicinal chemists for the desired modifications of leads for clinical drug candidates. SERMs, ought to produce inhibitory activity in breast, uterus and agonist activity in other tissues, are beneficial for estrogen-like actions.

Estrogen signaling: An emanating therapeutic target for breast cancer treatment.

Breast cancer, a most common malignancy in women, was known to be associated with steroid hormone estrogen. The discovery of estrogen receptor (ER) gave us not only a powerful predictive and prognostic marker, but also an efficient target for the treatment of hormone-dependent breast cancer with various estrogen ligands. ER consists of two subtypes i.

Protein-Protein Interactions and Aggregation Inhibitors in Alzheimer's Disease.

Background: Alzheimer's Disease (AD), a multifaceted disorder, involves complex pathophysiology and plethora of protein-protein interactions. Thus such interactions can be exploited to develop anti-AD drugs.

Objective: The interaction of dynamin-related protein 1, cellular prion protein, phosphoprotein phosphatase 2A and Mint 2 with amyloid β, etc.

Biomolecular basis of matrix metallo proteinase-9 activity.

Matrix metalloproteinases (MMPs) are structurally related endopeptidases. They are also known as metzincins due to their interaction with zinc ion of the conserved methionine (Met) at the active site. MMPs play an important role in physiological and signaling processes of wound healing, bone resorption and angiogenesis.