Exploration of a Library of 3,4‐(Methylenedioxy)aniline‐Derived Semicarbazones as Dual Inhibitors of Monoamine Oxidase and Acetylcholinesterase: Design,Synthesis, and Evaluation

A library of 3,4‐(methylenedioxy)aniline‐derived semicarbazones was designed, synthesized, and evaluated as monoamine oxidase (MAO) and acetylcholinesterase (AChE) inhibitors for the treatment of neurodegenerative diseases. Most of the new compounds selectively inhibited MAO‐B and AChE, with IC₅₀ values in the micro‐ or nanomolar ranges. Compound 16 , 1‐(2,6‐dichlorobenzylidene)‐4‐(benzo[1,3]dioxol‐5‐yl)semicarbazide presented a balanced multifunctional profile of MAO‐A (IC₅₀=4.52±0.032 μm ), MAO‐B (IC₅₀=0.059±0.002 μm ), and AChE (IC₅₀=0.0087±0.0002 μm ) inhibition without neurotoxicity. Kinetic studies revealed that compound 16 exhibits competitive and reversible inhibition against MAO‐A and MAO‐B, and mixed‐type inhibition against AChE. Molecular docking studies further revealed insight into the possible interactions within the enzyme–inhibitor complexes. The most active compounds were found to interact with the enzymes through hydrogen bonding and hydrophobic interactions. Additionally, in silico molecular properties and ADME properties of the synthesized compounds were calculated to explore their drug‐like characteristics.     

Multi Response Optimization on Machinability of SiC Waste Fillers Reinforced Polymer Matrix Composite Using Taguchi’s Coupled Grey Relational Analysis

Silicon - Recycling and reutilization of industrial waste is one way to minimize land pollution to attain green environment. In this research waste SiC grinding wheel was ball milled to powder form...     

Development of a method employing reversed‐phase thin‐layer chromatography for establishing milk fat purity with respect to adulteration with vegetable oils

A systematic study was conducted using reversed‐phase thin‐layer chromatography wherein unsaponifiable matter of samples namely, pure cow and buffalo milk fats, vegetable oils (groundnut oil, soya bean oil and sunflower oil) and milk fats adulterated with vegetable oils (≥1%) were run along with the reference standards using two new solvent systems to detect adulteration in milk fat. The results of the study revealed that adulteration at even a 1% level could easily be detected using this rapid, reliable and reproducible method based on the presence of β‐sitosterol as a marker and some additional spots ascribable to their occurrence in vegetable oils only.     

Antibiotic susceptibility profiles of new probiotic Lactobacillus and Bifidobacterium strains

The antimicrobial susceptibilities and presence of plasmids in four new probiotic lactic acid bacteria (LAB) strains, Lactobacillus rhamnosus HN001 (DR20) HN067, Lactobacillus acidophilus HN017 and Bifidobacterium lactis HN019 (DR10), were determined. Resistance to 18 commonly used antibiotics was assessed by disk diffusion. The three Lactobacillus strains had similar antibiotic susceptibility profiles to those of Lactobacillus plantarum strain HN045 and two commercial probiotic Lactobacillus strains, GG and LA-1. The B. lactis strain HN019 had a similar profile to three commercial probiotic B. lactis strains (Bb12, HN049 and HN098). All 10 strains were sensitive to the Gram-positive spectrum antibiotics erythromycin and novobiocin, the broad-spectrum antibiotics rifampicin, spectinomycin, tetracycline and chloramphenicol and the beta-lactam antibiotics penicillin, ampicillin and cephalothin. By contrast, most strains were resistant to the Gram-negative spectrum antibiotics fusidic acid, nalidixic acid and polymyxin B and the aminoglycosides neomycin, gentamicin, kanamycin and streptomycin. All three L. rhamnosus strains (HN001, HN067 and GG) were resistant to vancomycin and several strains were also resistant to cloxacillin. Of the four new probiotic strains, only L. rhamnosus HN001 contained plasmids; however, a plasmid-free derivative of HN001 had the same antibiotic susceptibility profile as the parent strain.     

Effect of Repetitive Lysine-Tryptophan Motifs on the Eukaryotic Membrane

In a previous study, we synthesized a series of peptides containing simple sequence repeats, (KW)_n–NH₂ (n = 2,3,4 and 5) and determined their antimicrobial and hemolytic activities, as well as their mechanism of antimicrobial action. However, (KW)₅ showed undesirable cytotoxicity against RBC cells. In order to identify the mechanisms behind the hemolytic and cytotoxic activities of (KW)₅, we measured the ability of these peptides to induce aggregation of liposomes. In addition, their binding and permeation activities were assessed by Trp fluorescence, calcein leakage and circular dichrorism using artificial phospholipids that mimic eukaryotic liposomes, including phosphatidylcholine (PC), PC/sphingomyelin (SM) (2:1, w/w) and PC/cholesterol (CH) (2:1, w/w). Experiments confirmed that only (KW)₅ induced aggregation of all liposomes; it formed much larger aggregates with PC:CH (2:1, w/w) than with PC or PC:SM (2:1, w/w). Longer peptide (KW)₅, but not (KW)₃ or (KW)₄, strongly bound and partially inserted into PC:CH compared to PC or PC:SM (2:1, w/w). Calcein release experiments showed that (KW)₅ induced calcein leakage from the eukaryotic membrane. Greater calcein leakage was induced by (KW)₅ from PC:CH than from PC:SM (2:1, w/w) or PC, whereas (KW)₄ did not induce calcein leakage from any of the liposomes. Circular dichroism measurements indicated that (KW)₅ showed higher conformational transition compared to (KW)₄ due to peptide-liposome interactions. Taken together, our results suggest that (KW)₅ reasonably mediates the aggregation and permeabilization of eukaryotic membranes, which could in turn explain why (KW)₅ displays efficient hemolytic activity.     

PG-2, a Potent AMP against Pathogenic Microbial Strains,from Potato (Solanum tuberosum L cv. Gogu Valley) Tubers Not Cytotoxic against Human Cells

In an earlier study, we isolated potamin-1 (PT-1), a 5.6-kDa trypsin-chymotrypsin protease inhibitor, from the tubers of a potato strain (Solanum tuberosum L cv. Gogu Valley). We established that PT-1 strongly inhibits pathogenic microbial strains, but not human bacterial strains, and that its sequence shows 62% homology with a serine protease inhibitor. In the present study, we isolated an antifungal and antibacterial peptide with no cytotoxicity from tubers of the same potato strain. The peptide (peptide-G2, PG-2) was isolated using salt-extraction, ultrafiltration and reverse-phase high performance liquid chromatography (RP-HPLC). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) showed the protein to have a molecular mass of 3228.5 Da, while automated Edman degradation showed the N-terminal sequence of PG-2 to be LVKDNPLDISPKQVQALCTDLVIRCMCCC-. PG-2 exhibited antimicrobial activity against Candida albicans, a human pathogenic yeast strain, and Clavibacter michiganensis subsp. michiganensis, a plant late blight strain. PG-2 also showed antibacterial activity against Staphylococcus aureus, but did not lyse human red blood cells and was thermostable. Overall, these results suggest PG-2 may be a good candidate to serve as a natural antimicrobial agent, agricultural pesticide and/or food additive.     

Excipients in parenteral formulations: selection considerations and effective utilization with small molecules and biologics

Excipients form a major component of pharmaceutical formulations and are classified as any ingredient other than the active ingredient which is included within the product formulation to improve drug product performance. Functional uses of excipients include improving solubility and stability, safety and efficacy, as bulking agents in lyophilized formulations, tonicity agents, and aiding in controlled or prolonged drug delivery. Parenteral formulations are sterile, pyrogen-free; free of particulate matter and by-pass the body’s natural defense mechanisms. Excipients may demonstrate a synergistic effect when combined with an active ingredient but may also lead to unwanted reactions with the drugs and packaging components. Ideal excipients are required to be considered safe, inert and multifunctional. Contrary to the past, safety of excipients needs to be well established in order for their use in the pharmaceutical formulations. Therefore, careful consideration should be given while selecting an excipient. This review article provides an overview of the excipients used exclusively in small molecule and biological parenteral products including solutions, suspensions, and lyophilized formulations, information on the possible drug-excipient and drug-packaging interactions and the regulatory requirements for the use of pharmaceutical excipients. The readers will be able to have a comprehensive understanding of the excipients used in parenteral formulations.