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Protein synthesis | Define Protein synthesis at …
The aim of the current study was the design andsynthesis of 5-mercapto-1,2,4-triazole derivatives with eventuallypredicted antiproliferative and antibacterian properties; theantitumor activity is tentatively exerted through the inhibition ofPI3K protein, as established by means of molecular docking. Thebiological activity of the identified triazole compounds wasevaluated on tumor cell lines, and on severalbacterial strains, respectively.
PI3K is the enzyme that catalyzes the formation ofphosphatidylinositol 3,4,5-trisphosphate (PIP3) fromphosphatidylinositol 4,5-bisphosphate (PIP2) (). PIP3 is responsible for theactivation of the enzyme, AKT, a serine/threonine-specific proteinkinase which phosphorylates downstream effectors within cellsurvival, proliferation and metabolic pathways (–).One of these effectors is mTOR, a serine/threonine protein kinasefrom the phosphatidylinositol 3-kinase-related kinases (PIKK)family which modulates protein synthesis via the regulation of thephosphorylation state of translational proteins (), such as p70 ribosomal S6 kinase(P70S6K) and eukaryotic translation initiation factor 4E-bindingprotein 1 (4E-BP1) ().
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In conclusion, in the present study, we describedthe design and synthesis of three triazole derivatives withantibacterial and antiproliferative activity. The three evaluatedstructures emerged as a result of molecular docking which indicateda highly favorable accommodation within the active binding site ofPI3K protein, thus acting as PI3K inhibitors and interfering withthe PI3K/AKT pathway, a signaling cascade present in numerous typesof cancer. The three compounds acted as antitumor agents againsttriple negative breast cancer (MDA-MB-231 cell line) and exhibitedlow toxicity and good selectivity thus offering promisingperspectives in anticancer therapy.
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