Development of novel isatin thiazolyl-pyrazoline hybrids as promising antimicrobials in MDR pathogens

Microbial Multidrug Resistance (MDR) is an emerging global crisis. Derivatization of natural or synthetic scaffolds is among the most reliable strategies to search for and obtain novel antimicrobial agents for the treatment of MDR infections. Here, we successfully manipulated the synthetically flexible isatin moieties to synthesize 22 thiazolyl-pyrazolines hybrids, and assessed their potential antimicrobial activities in vitro against various MDR pathogens, using the broth microdilution calorimetric XTT reduction method. We chose 5 strains to represent the major MDR microorganisms, viz: Methicillin resistant S. aureus (MRSA), and Vancomycin-resistant E. faecalis (VRE) as Gram-positive bacteria; Carbapenem-resistant K. pneumonia (CRKP), and Extended-spectrum beta-lactamase E. coli (ESBL-E), as Gram-negative bacteria; and Fluconazole-resistant C. albicans (FRCA), as a yeast-like unicellular fungus.The cytotoxicity of compounds 9f and 10h towards mammalian lung fibroblast (MRC-5) cells demonstrated their potential satisfactory safety margin as represented by their relatively high IC50 values. The target compounds showed promising anti-MDR activities, suggesting they are potential leads for further development and in vivo studies

Outgoing and potential trends of the omega-3 rich linseed oil quality characteristics and rancidity management: A comprehensive review for maximizing its food and nutraceutical applications

Background: Linseed or flaxseed (Linum usitatissimum L) is an ancient perennial plant species regarded as a multipurpose plant mostly due to its seed unique richness in omega-3 fatty acids. The extensive biochemical analysis of linseed further resulted in the identification of its other components i.e., lignans with potential applications in the improvement of human health. Linseed oil that amount for 40% of its seed weight is an edible oil in demand as a dietary supplement owing to its several health benefits. Scope and approach: This comprehensive review based on research papers and patents capitalizes on linseed oil, the major product of linseed with emphasis on the interrelationship between extraction methods, holistic chemical composition, sensory characters, and nutritional value. Overview of the different analytical approaches for linseed oil analysis and its quality control assessment is presented i.e., adulteration detection highlighting for each application advantages and limitations. Key findings and conclusions: Different oil extraction as well as processing methods are reviewed and in context to their influence on the final oil quality and/or biological effects. The review recapitulates on the rancidity prevention approaches to ensure best oil quality and shelf life. The extraction method as well as the pretreatments appeared to dramatically affect the yield and the quality of the oil

Overview of the Molecular Modalities and Signaling Pathways Intersecting with β-Amyloid and Tau Protein in Alzheimer’s Disease

Alzheimer’s disease (AD) is one of the major causes of dementia and its incidence represents approximately 60–70% of all dementia cases worldwide. Many theories have been proposed to describe the pathological events in AD, including deterioration in cognitive function, accumulation of β-amyloid, and tau protein hyperphosphorylation. Infection as well as various cellular molecules, such as apolipoprotein, micro-RNA, calcium, ghrelin receptor, and probiotics, are associated with the disruption of β-amyloid and tau protein hemostasis. This review gives an overview on the integrative cellular and signaling molecules that could play a complementary role in the dysregulation of β-amyloid and tau proteins

Design, biological evaluation, and molecular modelling insights of cupressic acid derivatives as promising anti-inflammatory agents

AbstractThe major labdanes in the oleogum resin of Araucaria heterophylla (Salisb.) Franco, 13-epi-cupressic acid (1) and acetyl-13-epi-cupressic acid (2) were used to prepare seven new (3–9), along with one known (10) derivatives. RAW264.7 cells were used to evaluate the anti-inflammatory activity of the derivatives (1–10) via measuring the level of COX-2 expression and IL-6. Pre-treated RAW264.7 cells with 1–10 (except for derivative 7) at 25 µM for 24h exhibited downregulation of COX-2 expression in response to LPS stimulation. Moreover, pre-treatment with compounds 1, 2, or 3 significantly attenuated the LPS-stimulated IL-6 level in RAW264.7 cells (p < 0.05). A docking study was conducted against phospholipase A2 (PLA2), a crucial enzyme in initiating the inflammatory cascade. The significant structural features of compounds (1–10) as PLA2 inhibitors included the carbonyl group at C-4 (free or substituted) and the hydrophobic diterpenoid skeleton. This study suggested 13-epi-cupressic acid as a scaffold for new anti-inflammatory agents

Derivatization, molecular docking and <i>in vitro</i> acetylcholinesterase inhibitory activity of glycyrrhizin as a selective anti-Alzheimer agent

<p>Acetylcholinesterase inhibitors (AChE-Is) increase both level and duration of action of acetylcholine (ACh); thus, alleviate symptoms of Alzheimer’s disease (AD). Glycyrrhizin, is the main active compound in liquorice root. Its aglycone, glycyrrhetinic acid, has shown several beneficial pharmacological activities. This study reports the synthesis and screening of a series of glycyrrhetinic acid analogs as AChE-Is. Fourteen derivatives were prepared, of which five derivatives are recorded as new viz., 3-phenyl-carbamoyl-18β-glycyrrhetinic acid (<b>J9</b>), 3-acetyl-18β-glycyrrhetinic-30-anilinamide (<b>J10</b>), 3-acetyl-18β-glycyrrhetinic-30-ethanolamide (<b>J11</b>), 3-acetyl-18β-glycyrrhetinic-30-<i>n</i>-butylamide (<b>J12</b>) and 18β-glycyrrhetinic acid-30-prenyl ester (<b>J14</b>), in addition to nine known derivatives (<b>J1</b>-<b>J8</b> & <b>J13</b>). Compounds <b>J12, J11, J0</b> and <b>J3</b> showed remarkable AChE-I activity with IC₅₀ values of 3.43, 5.39, 6.27 and 8.68 μM, respectively. These results are in full agreement with the docking study. The active compounds were non-cytotoxic to normal cells (WI-38).</p

Derivatization, molecular docking and <i>in vitro</i> acetylcholinesterase inhibitory activity of glycyrrhizin as a selective anti-Alzheimer agent

<p>Acetylcholinesterase inhibitors (AChE-Is) increase both level and duration of action of acetylcholine (ACh); thus, alleviate symptoms of Alzheimer’s disease (AD). Glycyrrhizin, is the main active compound in liquorice root. Its aglycone, glycyrrhetinic acid, has shown several beneficial pharmacological activities. This study reports the synthesis and screening of a series of glycyrrhetinic acid analogs as AChE-Is. Fourteen derivatives were prepared, of which five derivatives are recorded as new viz., 3-phenyl-carbamoyl-18β-glycyrrhetinic acid (<b>J9</b>), 3-acetyl-18β-glycyrrhetinic-30-anilinamide (<b>J10</b>), 3-acetyl-18β-glycyrrhetinic-30-ethanolamide (<b>J11</b>), 3-acetyl-18β-glycyrrhetinic-30-<i>n</i>-butylamide (<b>J12</b>) and 18β-glycyrrhetinic acid-30-prenyl ester (<b>J14</b>), in addition to nine known derivatives (<b>J1</b>-<b>J8</b> & <b>J13</b>). Compounds <b>J12, J11, J0</b> and <b>J3</b> showed remarkable AChE-I activity with IC₅₀ values of 3.43, 5.39, 6.27 and 8.68 μM, respectively. These results are in full agreement with the docking study. The active compounds were non-cytotoxic to normal cells (WI-38).</p