Browsing by Author "Stefanova D."

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    EVALUATION OF THE IN VITRO NEUROTOXIC AND NEUROPROTECTIVE EFFECTS AT CELLULAR AND SUBCELLULAR LEVELS OF NEWLY SYNTHESIZED N-PYRROLYL HYDRAZONES
    (2022-01-01) Tzankova D.; Vladimirova S.; Stefanova D.; Peikova L.; Kondeva-Burdina M.; Georgieva M.
    The study presents the safety, antioxidant activity and neuroprotective effects of a series of newly synthesized N-pyrrolyl hydrazide-hydrazones (5, 5a-g) in two in vitro models: human neuronal cells SH-SY5Y and isolated rat brain synaptosomes. The performed in vitro toxicological evaluation in neuronal SH-SY5Y cell line models determined the lowest cytotoxicity and best safety profile for compound 5a, followed by 5d on both evaluated parameters. The protective effect of the newly synthesized hydrazone 5a was found to be comparable to melatonin used as a standard. The obtained results indicate that the presence of pyrrole ring, containing multiple phenyl nuclei and hydrazide-hydrazone group in the side chain, leads to increase in the antioxidant effect.
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    New Indole-3-Propionic Acid and 5-Methoxy-Indole Carboxylic Acid Derived Hydrazone Hybrids as Multifunctional Neuroprotectors
    (2023-04-01) Anastassova N.; Stefanova D.; Hristova-Avakumova N.; Georgieva I.; Kondeva-Burdina M.; Rangelov M.; Todorova N.; Tzoneva R.; Yancheva D.
    In light of the known neuroprotective properties of indole compounds and the promising potential of hydrazone derivatives, two series of aldehyde-heterocyclic hybrids combining those pharmacophores were synthesized as new multifunctional neuroprotectors. The obtained derivatives of indole-3-propionic acid (IPA) and 5-methoxy-indole carboxylic acid (5MICA) had good safety profiles: Hemolytic effects < 5% (200 μM) and IC50 > 150 µM were found in the majority of the SH-SY5Y and bEnd3 cell lines. The 2,3-dihydroxy, 2-hydroxy-4-methoxy, and syringaldehyde derivatives of 5MICA exhibited the strongest neuroprotection against H2O2-induced oxidative stress in SH-SY5Y cells and 6-OHDA-induced neurotoxicity in rat-brain synaptosomes. All the compounds suppressed the iron-induced lipid peroxidation. The hydroxyl derivatives were also the most active in terms of deoxyribose-degradation inhibition, whereas the 3,4-dihydroxy derivatives were able to decrease the superoxide-anion generation. Both series of compounds showed an increased inhibition of hMAO-B, with greater expression detected in the 5MICA hybrids. The in vitro BBB model with the bEnd3 cell line showed that some compounds increased the permeability of the endothelial monolayer while maintaining the tight junctions. The combined results demonstrated that the derivatives of IPA and 5MICA showed strong neuroprotective, antioxidant, MAO-B inhibitory activity and could be considered as prospective multifunctional compounds for the treatment of neurodegenerative disorders.