The spiro[pyrrolidine-3, 3´-oxindole] moiety is present as a core in number of alkaloids with substantial biological activities. Here in we report design and synthesis of a library of compounds bearing spiro[pyrrolidine-3, 3´-oxindole] motifs that demonstrated exceptional inhibitory activity against the proliferation of MCF-7 breast cancer cells. The synthesis involved a one pot Pictet Spengler-Oxidative ring contraction of tryptamine to the desired scaffolds and occurred in 1:1 THF and water with catalytic trifluoroacetic acid and stoichiometric N-bromosuccinimide as an oxidant. Phenotypic profiling indicated that these molecules induce apoptotic cell death in MCF-7 cells. Target deconvolution with most potent compound 5l from the library, using chemical proteomics indicated histone deacetylase 2 (HDAC2) and prohibitin 2 as the potential cellular binding partners. Molecular docking of 5l with HDAC2 provided insights pertinent to putative binding interactions.
We present methods for limited-resource-friendly preparation of chitosan magnetic particles that are amenable to ultrasensitive downstream isothermal and conventional nucleic acid amplification tests.
Fabricated an inexpensive bi-electrode electrochemical sensor for nucleic acid amplification detection with a user-friendly interface in a short detection time.Electronic conduction of the metal oxide sensing layer was successfully optimised by manipulating the concentration of oxygen vacancies.The sensing layer was annealed at various temperatures and optimised by testing their electrical, optical, and chemical properties.The fabricated device was able to detect dengue virus sequence DNA and Staphylococcus aureus genomic DNA with clinically relevant limit of detection.
Bioisosteric modification of known fucosidase inhibitors A and B, resulted in three new types of molecules, 4b, 5c and 6a (belonging to furopyridinedione, thiohydantoin and hydantoin chemotypes) that could potentially bind to a-L-fucosidase (bovine kidney origin). Molecular docking revealed and compared the putative binding interaction between 4b, 5c and 6a with A and B against the active site of a homology model of a-L-fucosidase. Based on this initial investigation, design and synthesis of a library of small molecules based on furopyridinedione, thiohydantoin and hydantoin, followed by their in vitro screening against a-L-fucosidase (bovine kidney origin) generated a potent inhibitor (compound 4e) with IC 50 of $0.7 mM. Compound 4e possessed no cytotoxic properties when tested against healthy mammalian COS-1 cells. Reaction kinetics study suggested it to be a mixed inhibitor. Finally compounds 4a, b, e and f, bearing the furopyridinedione motif also exhibited substantial inhibition of the proliferation of MCF 7 breast cancer cells.
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