Synthesis and Evaluation of 2, 5-substituted Pyrazolone for Neuroprotective Potential in SH-SY5Y Human Neuroblastoma Cells

被引:0
作者
Manikandan, R. [1 ]
Devi, K. [1 ]
Rajalingam, D. [2 ]
机构
[1] Annamalai Univ, Dept Pharm, Chidambaram, Tamil Nadu, India
[2] Kamalakshi Pandurangan Coll Pharm, Dept Pharmaceut Chem, Tiruvannamalai, Tamil Nadu, India
关键词
Cell viability; MTT assay; Neurodegenerative diseases; Neuroprotective agent; Pyrazole derivatives; SH-SY5Y cells; ALZHEIMERS-DISEASE; MONOAMINE-OXIDASE; 1-N-SUBSTITUTED THIOCARBAMOYL-3-PHENYL-5-THIENYL-2-PYRAZOLINES; MITOCHONDRIAL DYSFUNCTION; INDUCED APOPTOSIS; B INHIBITORS; BETA; DEATH; DEGENERATION; ANTIOXIDANT;
D O I
10.5530/ijper.20256349
中图分类号
G40 [教育学];
学科分类号
040101 ; 120403 ;
摘要
Aim: To carry out Synthesis and Evaluation of novel 2, 5-substituted Pyrazolone for Alzheimer's Disease (AD) has become a serious public health concern as a result of people living longer than ever before. It is critically necessary to discover a way to halt and postpone the illness. The present study aims to determine if new synthetic analogue pyrazole derivatives may protect against toxicity caused by A(325-35 and its underlying mechanisms in neuroblastoma cells like SH-SY5Y. PyRx 0.9 software was used for molecular docking studies. The cells of SH-SY5Y were preincubated for 30 min with varying doses of the generated compounds (C1-C10) to induce neurotoxicity. They were then grown in A(325-35 (25 mol/L) for 48 hr. Cell viability was determined by MTT assay. Results: Compounds C5 and C8 exhibited a better binding score -8.4k/ cal compared to other analogues. Synthesized compounds C5 and C8 inhibited A(325-35-induced apoptosis in SH-SY5Y cells and protected neural cells from damage. Conclusion: The MTT assay confirmed that compounds C5 and C8 significantly reduced A(325-35-induced toxicity among human neuroblastoma SH-SY5Y cells, demonstrating its neuroprotective properties.
引用
收藏
页码:s323 / s332
页数:10
相关论文
共 39 条
  • [1] Famer D, Crisby M., Rosuvastatin reduces caspase-3 activity and up regulate sa-secretase in human neuroblastoma SH-SY5Y cells exposed to Ab, Neuro sci Lett, 371, pp. 209-214, (2004)
  • [2] Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K, Et al., Amyloid plaque core protein in Alzheimer’s disease and Down syndrome, Proc Natl Acad Sci USA, 82, pp. 4245-4249, (1985)
  • [3] Hardy JA, Higgins GA., Alzheimer’s disease: the amyloid cascade hypothesis, Sci, 256, pp. 184-185, (1992)
  • [4] Selkoe DJ., Amyloid beta-protein and the genetics of Alzheimer’s disease, J Biol Chem, 271, pp. 18295-18298, (1996)
  • [5] Butterfiled DA, Castegna A, Lauderback CM, Drake J., Evidence that amyloid b-peptide-induced lipid peroxidation and its equelae in Alzheimer’s disease brain contribute to neuronal death, Neuro biol Aging, 23, pp. 655-664, (2002)
  • [6] Wang R, Zhang HY, Tang XC., Huperzine A attenuates cognitive dysfunction and neuronal degeneration caused by b-amyloid protein-(1-40) in rat, Eur J Pharmacol, 421, pp. 149-156, (2001)
  • [7] Eckert A, Keil U, Marques CA, Bonert A, Frey C, Schussel K, Et al., Mitochondrial dysfunction, apoptotic cell death and Alzheimer’s disease, Biochem Pharmacol, 66, pp. 1627-1634, (2003)
  • [8] Xu J, Chen S, Ku G, Ahmed SH, Xu J, Chen H, Et al., Amyloid beta peptide-induced cerebral endothelial cell death involves mitochondrial dysfunction and caspase activation, J Cereb Blood Flow and Metab, 21, pp. 702-710, (2001)
  • [9] Loo D T, Copani A, Pike CJ, Whittemore ER, Walencewicz AJ, Cotman CW., Apoptosis is induced by b-amyloid in cultured central nervous system neurons, Proc Natl Acad Sci USA, 90, pp. 7951-7955, (1993)
  • [10] Thompson CB., Apoptosis in the pathogenesis and treatment of disease, Sci, 267, pp. 1456-1462, (1995)