Sesquiterpene metabolites from Pogostemon cablin leaf essential oil as acetylcholinesterase inhibitors: An integrated computational and phytochemical study.

Neurological disorders are the major factor of dementia worldwide, presenting significant and escalating challenges to global healthcare systems. Alzheimer's disease (AD) is a leading cause of dementia, creating substantial challenges for international healthcare. Medicinal and aromatic plants offer diverse pharmaceutical properties owing to their richness in chemical constituents.

In Vitro and In Silico Approaches to Exploring the Potential Therapeutic Effects of Curcuma amada Rhizome Essential Oil.

Curcuma amada (mango ginger) is a medicinal herb valued for its traditional uses and pharmacological properties. This study investigates the essential oil (EO) from C. amada rhizome (Curcuma amada rhizome EO [CAREO]), highlighting its anti-microbial, anti-diabetic, and anti-inflammatory activities through in vitro and in silico methods.

Network pharmacology-integrated molecular modeling analysis of L. (agarwood) essential oil phytocompounds.

A network pharmacology approach was used to construct comprehensive pharmacological networks, elucidating the interactions between agarwood compounds and key biological targets associated with cancer pathways. We have employed a combination of network pharmacology, molecular docking and molecular dynamics to unravel agarwood plants' active components and potential mechanisms. Reported 23 molecules were collected from the agarwood plants and considered to identify molecular targets.

Assessment of Bioactivity of Homalomena aromatica Essential Oil From Northeast India Through Combinative In Vitro and In Silico Approaches.

Homalomena aromatica Schott is a valuable medicinal aromatic plant having wide range of applications in ethnobotany, pharmacology, perfumery and flavor industry. Traditionally, various part of H. aromatica such as leaves and rhizomes were applied to treat joint pain, skin diseases, colds, asthma, diarrhea, and jaundice.

Designing of potent anti-diabetic molecules by targeting SIK2 using computational approaches.

Diabetes mellitus (DM) is one of the major health problems worldwide. WHO have estimated that 439 million people may have DM by the year 2030. Several classes of drugs such as sulfonylureas, meglitinides, thiazolidinediones etc.

WaterMap and Molecular Dynamic Simulation-Guided Discovery of Potential PAK1 Inhibitors Using Repurposing Approaches.

p21-Activated kinase 1 (PAK1) is positioned at the nexus of several oncogenic signaling pathways. Currently, there are no approved inhibitors for disabling the transfer of phosphate in the active site directly, as they are limited by lower affinity, and poor kinase selectivity. In this work, a repurposing study utilizing FDA-approved drugs from the DrugBank database was pursued with an initial selection of 27 molecules out of ∼2162 drug molecules, based on their docking energies and molecular interaction patterns.

Water Mapping and Scoring Approaches to Predict the Role of Hydration Sites in the Binding Affinity of PAK1 Inhibitors.

Aim: This study aims to develop and establish a computational model that can identify potent molecules for p21-activating kinase 1 (PAK1) Background: PAK1 is a well-established drug target that has been explored for various therapeutic interventions. Control of this protein requires an indispensable inhibitor to curb the structural changes and subsequent activation of signalling effectors responsible for the progression of diseases, such as cancer, inflammatory, viral, and neurological disorders.

Objective: The study aims to establish a computational model that could identify active molecules which will further provide a platform for developing potential PAK1 inhibitors.

Discovery of potent Camkk1 kinase inhibitors through e-pharmacophore and molecular screening approaches.

Diabetes is recognized as a major health problem and according to WHO estimates global prevalence of diabetes is expected to increase from 171 million in 2000 to 366 million in 2030, among which 21.7% will be Indians. The chronic nature of diabetes leads to several metabolic complications like kidney failure, cardiac problems and hypertension, etc.

Structural insights on binding mechanism of CAD complexes (CPSase, ATCase and DHOase).

Pyrimidine biosynthetic pathway enzymes constitute an important target for the development of antitumor drugs. To understand the role of binding mechanisms underlying the inborn errors of pyrimidine biosynthetic pathway, structure and function of enzymes have been analyzed. Pyrimidine biosynthetic pathway is initiated by CAD enzymes that harbor the first three enzymatic activities facilitated by Carbamoyl Phosphate Synthetase (CPSase), Aspartate Transcarbamoylase (ATCase) and Dihydroorotase (DHOase).

Design of novel MTNA inhibitors, targeting neurological disorder through homology modeling, molecular docking, and dynamics approaches.

Vanishing white matter (VWM) is a hereditary human disease, mostly prevalent in childhood caused by the defects in the eukaryotic initiation factor beta subunits. It is the first disease involved in the translation initiation factor, eIF2B. There is no specific treatment for VWM which mainly affect the brain and ovaries.

Identification of Pak1 inhibitors using water thermodynamic analysis.

p21-activated kinases (Paks) play an integral component in various cellular diverse processes. The full activation of Pak is dependent upon several serine residues present in the N-terminal region, a threonine present at the activation loop, and finally the phosphorylation of these residues ensure the complete activation of Pak1. The present study deals with the identification of novel potent candidates of Pak1 using computational methods as anti-cancer compounds.

Molecular mechanism of anti-cancer activity of phycocyanin in triple-negative breast cancer cells.

Background: Triple-negative breast cancers represent an important clinical challenge, as these cancers do not respond to conventional endocrine therapies or other available targeted agents. Phycocyanin (PC), a natural, water soluble and non-toxic molecule is shown to have potent anti-cancer property.

Methods: In this study, we determined the efficacy of PC as an anti-neoplastic agent in vitro on a series of breast cancer cell lines.

Mechanical insights of oxythiamine compound as potent inhibitor for human transketolase-like protein 1 (TKTL1 protein).

Transketolase is a connecting link between glycolytic and pentose phosphate pathway, which is considered as the rate-limiting step due to synthesis of large number of ATP molecule and it can be proposed as a plausible target facilitating the growth of cancerous cells suggesting its potential role in cancer. Oxythiamine, an antimetabolite has been proved to be an efficient anticancerous compound in vitro, but its structural elucidation of the inhibitory mechanism has not yet been done against the human transketolase-like 1 protein (TKTL1). The three-dimensional (3D) structure of TKTL1 protein was modeled and subjected for refinement, stability and validation.

In silico analysis suggests that PH0702 and PH0208 encode for methylthioribose-1-phosphate isomerase and ribose-1,5-bisphosphate isomerase, respectively, rather than aIF2Bβ and aIF2Bδ.

The overall process of protein biosynthesis across all domains of life is similar; however, detailed insights reveal a range of differences in the proteins involved. For decades, the process of protein translation in archaea has been considered to be closer to eukaryotes than to bacteria. In archaea, however, several homologues of eukaryotic proteins involved in translation initiation have not yet been identified; one of them being the initiation factor eIF2B consisting of five subunits (α, β, γ, δ and ε).