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Volume 7, Issue 6 (Suppl) J Alzheimers Dis Parkinsonism, an open access journal
ISSN: 2161-0460 Dementia 2017
October 16-18, 2017
ALZHEIMER’S DISEASE & DEMENTIA
October 16-18, 2017 | Rome, Italy
9th International Conference on
Neuroprotective activity of novel 1,2,4-triazine derivatives againstH2O2 andAβ-inducedneurotoxicity,
new leads for Alzheimer’s
Hamid Irannejad1,2 and Tuba Tuylu Kucukkilinc1,2
1Mazandaran University of Medical Sciences, Iran
2Hacettepe University, Turkey
Alzheimer’s disease (AD) is a neuropathologic disorder characterized by intracellular neurofibrillary tangles and amyloid
aggregates in the CNS. In recent years numerous approaches have been used to combat AD like small molecule inhibitors
of Aβ aggregation, anti-inflammatory agents, cholinesterase, a- and β-secretase. Herein, we report synthesis of some 5,6-diaryl-
1,2,4-triazines 3a-f and 8a-e as potential agents for treatment of AD. We evaluated them against both H2O2 and β-amyloid
induced toxicity in PC-12 and SH-SY5Y cells and the extent of cell viability and apoptosis were assessed during 24 and 48
h of treatment. All compounds showed significant neuroprotective activity with EC50 values ranging from 14-30 µM. Most
compounds could increase cell viability compared to amyloid treated group. Surprisingly, 3-thioxo-1,2,4-triazin-2(3H)-yl)
acetate derivative 8e was the most potent compound in both tests with EC50 of 14 µM in H2O2 induced apoptosis and could
increase 40% of cell viability revealed by cytometric analysis with Annexin V/PI staining. It was also shown that 8e has more
neuroprotective activity than Quercetin in beta-amyloid induced toxicity. Moreover, compound 8e attenuated late-apoptosis
from 42% to 6% (P<0.005) and 7% to 1% at 24 and 48 hour respectively compared to amyloid treated cells. Similarly, apoptosis
was reduced from 12% to 4% at 24 hours. LDH release was not changed at any time points, pointing anti-apoptotic effect of
compound 8e. Morphologic evaluation of cells by DAPI staining and TUNEL assay showed the effectiveness of this compound
to improve neurite outgrowth and to prevent apoptosis and DNA fragmentation in neuronal cells.
Biography
Hamid Irannejad has completed his Pharm.D at Kerman University of Medical Sciences and PhD at Tehran University of Medical Sciences, IRAN. Postdoctoral
studies was accomplished at University of Siena, Italy, under the supervision of Prof. Maurizio Botta. Currently, he is serving as an assistant professor at Mazandaran
University of Medical Sciences. He has published nearly 20 papers in reputed journals in the field of medicinal chemistry.
Hamid Irannejad et al., J Alzheimers Dis Parkinsonism 2017, 7:6(Suppl)
DOI: 10.4172/2161-0460-C1-034