Promising protein biomarkers in the early diagnosis of Alzheimer's disease.

Alzheimer's disease (AD) is an insidious, multifactorial disease that involves the devastation of neurons leading to cognitive impairments. Alzheimer's have compounded pathologies of diverse nature, including proteins as one important factor along with mutated genes and enzymes. Although various review articles have proposed biomarkers, still, the statistical importance of proteins is missing. Proteins associated with AD include amyloid precursor protein, glial fibrillary acidic protein, calmodulin-like skin protein, hepatocyte growth factor, matrix Metalloproteinase-2. These proteins play a crucial role in the AD hypothesis which includes the tau hypothesis, amyloid-beta (Aß) hypothesis, cholinergic neuron damage, etc. The present review highlights the role of major proteins and their physiological functions in the early diagnosis of AD. Altered protein expression results in cognitive impairment, synaptic dysfunction, neuronal degradation, and memory loss. On the medicinal ground, efforts of making anti-amyloid, anti-tau, anti-inflammatory treatments are on the peak, having these proteins as putative targets. Few proteins, e.g., Amyloid precursor protein results in the formation of non-soluble sticky Aß40 and Aß42 monomers that, over time, aggregate into plaques in the cortical and limbic brain areas and neurogranin is believed to regulate calcium-mediated signaling pathways and thus modulating synaptic plasticity are few putative and potential forthcoming targets for developing effective anti-AD therapies. These proteins may help to diagnose the disease early, bode well for the successful discovery and development of therapeutic and preventative regimens for this devasting public health problem.

Identification and exploration of quinazoline-1,2,3-triazole inhibitors targeting EGFR in lung cancer.

Epidermal growth factor receptor (EGFR) enhances lung cancer development, due to their inability to permeate the cell membrane, secreted growth factors work through specialized signal transduction pathways. The purpose of this study is to find out a novel anticancer agent that inhibits EGFR and reduces the chances of lung cancer. A series of triazole-substituted quinazoline hybrid compounds were designed by Chemdraw software and docked against five different crystallographic EGFR tyrosine kinase domain (TKD). For docking and visualization PyRx, Autodock vina, and Discovery studio visualizer were used. Molecule-14, Molecule-16, Molecule-19, Molecule-20, and Molecule-38 showed significant affinity but Molecule-19 showed excellent binding affinity (-12.4 kcal/mol) with crystallographic EGFR tyrosine kinase. The superimposition of the co-crystalized ligand with the hit compound shows similar conformation at the active site of EGFR (PDB ID: 4HJO) indicating excellent coupling and pharmaceutically active. The hit compound showed a good bioavailability score (0.55) with no sign of carcinogenesis, mutagenesis, or reproductive toxicity properties. MD simulation and MMGBSA represent good stability and binding free energy demonstrating that the hit (Molecule-19) may be used as a lead compound. Molecule-19 also showed good ADME properties, bioavailability scores, and synthetic accessibility with fewer signs of toxicity. It was observed that Molecule-19 may be a novel and potential inhibitor against EGFR with fewer side effects than the reference molecule. Additionally, the molecular dynamics simulation revealed the stable nature of protein-ligand interaction and provided information about the amino acid residues involved in binding. Overall, this study led to the identification of potential EGFR inhibitors with favorable pharmacokinetic properties. We believe that the outcome of this study can help to develop more potent drug-like molecules to tackle human lung cancer.

Antiviral phytocompounds "ellagic acid" and "(+)-sesamin" of Bridelia retusa identified as potential inhibitors of SARS-CoV-2 3CL pro using extensive molecular docking, molecular dynamics simulation studies, binding free energy calculations, and bioactivity prediction.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected billions and has killed millions to date. Studies are being carried out to find therapeutic molecules that can potentially inhibit the replication of SARS-CoV-2. 3-chymotrypsin-like protease (3CL pro) involved in the polyprotein cleavage process is believed to be the key target for viral replication, and hence is an attractive target for the discovery of antiviral molecules. In the present study, we aimed to identify natural phytocompounds from Bridelia retusa as potential inhibitors of SARS-CoV-2 3CL pro (PDB ID: 6M2N) using in silico techniques. Molecular docking studies conducted with three different tools in triplicates revealed that ellagic acid (BR6) and (+)-sesamin (BR13) has better binding affinity than the co-crystal inhibitor "3WL" of 6M2N. BR6 and BR13 were found to have a high LD50 value with good bioavailability. 3WL, BR6, and BR13 bind to the same active binding site and interacted with the HIS41-CYS145 catalytic dyad including other crucial amino acids. Molecular dynamics simulation studies revealed stability of protein-ligand complexes as evidenced from root-mean-square deviations, root-mean-square fluctuations (RMSF), protein secondary structure elements, ligand-RMSF, protein-ligand contacts, ligand torsions, and ligand properties. BR6 (-22.3064 kcal/mol) and BR13 (-19.1274 kcal/mol) showed a low binding free energy value. The Bayesian statistical model revealed BR6 and BR13 as better protease inhibitors than 3WL. Moreover, BR6 and BR13 had already been reported to elicit antiviral activities. Therefore, we conclude that ellagic acid and (+)-sesamin as natural antiviral phytocompounds with inhibitory potential against SARS-CoV-2 3CL pro. Supplementary information: The online version contains supplementary material available at 10.1007/s11224-022-01959-3.

Physicochemical and disintegrant properties of glutinous rice starch of Mizoram, India.

The objective of the current work is to characterize the physicochemical and disintegrant properties of a starch obtained from a novel glutinous rice variety from Mizoram, India. Different properties such as total starch, apparent amylose content, protein and moisture content, along with micromeritic properties were evaluated. Viscosity was determined by Brookfield viscometer, DSC and FTIR spectroscopic analyses were also performed. The disintegrant efficiency was evaluated after dicalcium phosphate tablets were prepared using the starch as binder-disintegrant at different concentrations. The total starch content was found to be 83.48% with 2.83% crude protein and 10.22% moisture content. The average particle size of the starch was also found to be 11.39µm. DSC and FTIR analysis shows the starch possesses typical characteristics of starches. Results from disintegration efficiency study also showed that the starch possesses significant disintegration property and the disintegration efficiency increases with increase in concentration of the starch.

Exploitation of novel gum Prunus cerasoides as mucoadhesive beads for a controlled-release drug delivery.

The present study deals with the formulation of pH-sensitive mucoadhesive beads using natural gum isolated from Prunus cerasoides (PC) in combination with sodium alginate (SA) for the controlled release of diclofenac sodium (DS). PC and SA composite (PC-SA), DS loaded SA (DS-SA) and DS loaded PC-SA (DS-PC-SA) beads were prepared by ionotropic gelation method. The absence of interaction between DS and PC-SA was shown by FTIR, DSC and TGA analyses. The optimized DS-PC-SA formulation exhibited mucoadhesive property and the controlled release of DS was achieved 68% in 12h. The in vitro release kinetics follows zero order with anomalous diffusion mechanism. Therefore, the formulated mucoadhesive beads with the novel gum are preferable for the controlled release of DS by prolonging the residence time of the drug in the gastrointestinal tract, overcoming the problems associated with the immediate release dosage forms of DS.

Characterization and in vitro antioxidant activity of Albizia stipulata Boiv. gum exudates.

The objective of the present study is to characterize the physicochemical properties and to determine the in vitro antioxidant activity of Albizia stipulata Boiv. gum exudates collected from Northeast India. The total carbohydrate, uronic acid and protein contents, monosaccharide composition and the molecular weight distribution of the purified gum was determined. The powder flow property and preliminary compressibility test were performed on the dried gum exudates. Fourier transform infrared spectroscopy (FTIR) study was performed to analyze the functional groups present in the structure. Differential scanning calorimetry (DSC) and thermogravimetry (TGA/DTA) analyses were performed to study the thermal stability of the gum. The antioxidant properties of the gum were evaluated by determining 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl scavenging activities and reducing power. The total carbohydrate and protein contents of the gum were found to be 75.17±3.21% and 2.60±1.05% respectively. The viscosity of 2% aqueous solution of the gum exhibited non-Newtonian type of flow showing pH dependent swelling. Arabinose and galactose were found to be the main monosaccharides present in the gum exudates and the molecular weight distribution of the gum was also found to be polydispersed. Results from DPPH, hydroxyl scavenging and reducing power studies showed the gum possesses antioxidant properties.

Physicochemical characteristics and antioxidant activity of Prunus cerasoides D. Don gum exudates.

The physicochemical properties and antioxidant activity of Prunus cerasoides D. Don gum exudates was investigated in this study. The total carbohydrate and protein content were found to be 73.72±2.44% and 2.33±1.25%, respectively. Analysis of monosaccharide composition by HPLC-RI system after acid hydrolysis of the gum showed the presence of arabinose, galactose, glucose, rhamnose and xylose. The molecular weight of the gum was also found to be 5.55×10(5)Da. FTIR and DSC studies showed characteristics typical of a natural polysaccharide. The viscosity of 2% aqueous solution of the gum exhibited non-Newtonian type of flow and the gum was also found to show pH dependent swelling. Determination of the angle of repose, Carr's index and Hausner ratio indicate the gum possess fairly good powder flow property. The antioxidant properties of the gum were evaluated by determining DPPH and hydroxyl scavenging activities, reducing power and total phenolic contents which showed the gum possess antioxidant property.

Muli bamboo (Melocanna baccifera) as a new source of microcrystalline cellulose.

Microcrystalline cellulose (MCC) was prepared by hydrochloric acid hydrolysis from Muli bamboo (Melocanna baccifera) fibers to tap its potential as a green source of MCC. The cellulose and α-cellulose yield from the original material were 62.5 and 54.8 % respectively. The physicochemical properties of the prepared MCC were investigated using Avicel PH101 as a comparator. Micromeritic properties of the powder MCC samples were analyzed by determining its average particle size, flow properties, particle porosity and density. The total ash and moisture content along with the swelling index were also determined. The prepared MCC was also characterized by fourier transformed infrared spectroscopy (FTIR), scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and x-ray diffraction spectroscopy (XRD). Results from these analyses indicate that the Muli bamboo can be used as a green source of MCC.