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Alzheimer's disease (AD), a neurodegenerative disorder affects more than 35 million people globally. Acetylcholinesterase suppression is the common approach to enhance the well-being of AD patients by increasing the duration of acetylcholine in the cholinergic synapses. Generally, herbal secondary metabolites are reported to be a major resource for acetylcholinesterase inhibitors (AChEIs). Trans-tephrostachin was reported from Tephrosia purpurea for AChE inhibition. Here, we report on the design, synthesis, and assessment of human acetylcholinesterase inhibitory activity from trans-tephrostachin derivatives or analogs as anti-AD agents. The five newly synthesized compounds 4a. 4b, 4c, 4d and 4e displayed potent inhibitory activities with IC50 values of 35.0, 35.6, 10.6, 10.3, and 28.1 μM respectively. AChE enzyme kinetic study was performed for the five derived compounds using the Ellman's method. The Lineweaver-Burk and the secondary plots revealed the mixed inhibition for 4a, 4c and 4d whereas 4b and 4e demonstrated competitive inhibition. Molecular docking and molecular dynamics simulations showed the derivatives or analogs of trans-tephrostachin attained a high binding affinity and efficacy than the standard drug. In conclusion, trans-tephrostachin and its derivative compounds could become effective agents for further drug development to treat AD.

Marine cone snails are predatory gastropods characterized by a well-developed venom apparatus and highly evolved hunting strategies that utilize toxins to paralyze prey and defend against predators. The venom of each species of cone snail has a large number of pharmacologically active peptides known as conopeptides or conotoxins that are usually unique in each species. Nevertheless, venoms of only very few species have been characterized so far by transcriptomic approaches. In this study, we used transcriptome sequencing technologies and mass spectrometric methods to describe the diversity of venom components expressed by a worm-hunting species, Conus bayani. A total of 82 conotoxin sequences were retrieved from transcriptomic data that contain 54 validated conotoxin sequences clustered into 21 gene superfamilies including divergent gene family, 17 sequences clustered to 6 different conotoxin classes, and 11 conotoxins classified as unassigned gene family. Seven new conotoxin sequences showed unusual cysteine patterns. We were also able to identify 19 peptide sequences using mass spectrometry that completely overlapped with the conotoxin sequences obtained from transcriptome analysis. Importantly, herein we document the presence of 16 proteins that include five post-translational modifying enzymes obtained from transcriptomic data. Our results revealed diverse and novel conopeptides of an unexplored species that could be used extensively in biomedical research due to their therapeutic potentials.

Rhodamine based β-C-glycosides were synthesized through aldol condensation of β-C-glycosylketones with rhodamine aldehyde under ambient reaction conditions in good yields. Formation of the expected product has been confirmed through different spectral techniques. Gelation properties of these compounds were studied in regard to their molecular structure by HRTEM, FESEM. DSC, rheological and PXRD techniques. [ABSTRACT FROM AUTHOR]

A multicomponent one-pot reaction involving propargyl glycosides, fluorescein monoaldehyde, and aromatic amines using Cu(I) as catalyst is described, which provides an efficient and practical route for the synthesis of several fluorescein-based quinolone glycoconjugates in good yields. All of the synthesized quinoline glycoconjugates showed moderate antioxidant activity as evaluated with commercially available 1,1-diphenyl-2-picryl hydrazyl (DPPH). [ABSTRACT FROM AUTHOR]