ارزیابی ترکیبات 3 اکسو بوتان آمید در لنفوسیتهایی انسانی و میتو کندریهای ایزوله شده از آنها

سلیمی, احمد (1396) ارزیابی ترکیبات 3 اکسو بوتان آمید در لنفوسیتهایی انسانی و میتو کندریهای ایزوله شده از آنها. [ research project ]

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English Abstract

To reduce costly late-phase compound scrubbing, there has been an increased focus on assessing compounds within in vitro assays that predict properties of human safety liabilities, before preclinical in vivo studies. The aim of our study was to answer the questions that whether the toxicity risk of a series of 3-oxobutanamide derivatives could be predicted by using of human lymphocytes and their isolated mitochondria. Using biochemical and flow cytometry assessments, we demonstrated that exposure of lymphocytes and isolated mitochondria to five 3-oxobutanamide derivatives (1-5) did not exhibit remarkable toxicity at low concentrations (50-500μM) but toxicity could be observed at high concentrations (1000 and 2000μM), particularly for N-(5-(4-bromophenyl)-3-isoxazolyl)-3-oxobutanamide (4) and N-(2-benzothiazolyl)-3-oxo butanamide (5). Compounds 4, 5 and partly N-(5-methyl-3-isoxazol yl)-3-oxo butanamide (1) also showed a marked cellular and mitochondrial toxicity while compound 5 displayed superior toxicity. Compound 5 induced cytotoxicity on human blood lymphocytes which was associated with the generation of intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP) collapse, lysosomal membrane injury, lipid peroxidation and depletion of glutathione. Our results suggested that among assessed compounds, increased toxicity of compound 5 compared to other compounds could be likely attributed to the presence of bromine substituent in 5. Finally our findings proposed that using of antioxidants and mitochondrial/lysosomal protective agents could be beneficial in decreasing the toxicity of 5

Item Type: research project
زبان سند : فارسی
project status : اتمام یافته
مجری اصلی :احمد سلیمی
تاریخ اتمام :9 August 1396
Subjects:QV pharmacology > QV 600 Toxicology
QV pharmacology
Divisions:School of Pharmacy > Department of Toxicology
ID Code:9331
Deposited By: MS Soghra Golmaghani
Deposited On:09 Aug 1396 06:02
Last Modified:05 Oct 1397 08:54

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