Department of Biotechnology, College of Science and Humanities, SRM Institute of Science and Technology, Kattankulathur, 603 203 Chennai, Tamil Nadu, India.
Department of Chemistry, College of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, 603 203 Chennai, Tamil Nadu, India.
Life Sci. 2022 Jun 1;298:120507. doi: 10.1016/j.lfs.2022.120507. Epub 2022 Mar 28.
This study aims to elucidate a systematic free-radical quenching ability of synthesized benzo[b]thiophene derivatives using in vitro assays and acrylamide induced oxidatively stressed model in zebrafish larvae.
Antioxidant activity of the compounds was evaluated using in vitro methods. The toxicity of the compounds was evaluated in Madin-Darby Canine Kidney (MDCK) cell line and zebrafish embryos. Oxidative stress was generated by acrylamide (1 mM) in zebrafish larvae and treated with compounds to evaluate the in vivo antioxidant ability. Specific fluorescence dyes were used to detect ROS generation, lipid peroxidation, and cell death followed by gene expression using RT PCR. Density functional theory (DFT) and in silico pharmacokinetics were also studied.
Compound BP and EP have a greater in vitro free radical scavenging ability. The maximum tolerated concentration (MTC) of the compounds in zebrafish larvae is 80 μM. The antioxidant system in zebrafish larvae was dysregulated due to acrylamide exposure and improvement was found while treating acrylamide exposed larvae with compounds 1-(3-hydroxybenzo[b]thiophen-2-yl) ethanone (BP) and 1-(3-hydroxybenzo[b]thiophen-2-yl) propan-1-one hydrate (EP). Compound BP and EP enhanced the SOD and CAT activity, reduced the ROS and lipid peroxidation level, thus decreasing cell death in zebrafish larvae. Compound BP and EP also improved the glutathione redox cycle by stabilizing glutathione-related gene expressions.
Hydroxyl-containing compounds BP and EP are promising lead molecules for pathological conditions related to oxidative stress, which showed an attenuated effect on acrylamide-induced oxidative stress in zebrafish larvae by enhancing the glutathione redox cycle and enzymatic antioxidants.
本研究旨在通过体外试验和丙烯酰胺诱导的斑马鱼幼虫氧化应激模型阐明合成苯并[b]噻吩衍生物的系统自由基清除能力。
采用体外方法评价化合物的抗氧化活性。采用 Madin-Darby 犬肾 (MDCK) 细胞系和斑马鱼胚胎评价化合物的毒性。用丙烯酰胺（1 mM）在斑马鱼幼虫中产生氧化应激，并处理化合物以评估体内抗氧化能力。用特异性荧光染料检测 ROS 生成、脂质过氧化和细胞死亡，并用 RT-PCR 检测基因表达。还进行了密度泛函理论（DFT）和计算机药代动力学研究。
化合物 BP 和 EP 具有更强的体外自由基清除能力。化合物在斑马鱼幼虫中的最大耐受浓度（MTC）为 80 μM。由于丙烯酰胺暴露，斑马鱼幼虫的抗氧化系统失调，用化合物 1-(3-羟基苯并[b]噻吩-2-基)乙酮（BP）和 1-(3-羟基苯并[b]噻吩-2-基)丙-1-酮水合物（EP）处理丙烯酰胺暴露的幼虫后发现有所改善。化合物 BP 和 EP 增强了 SOD 和 CAT 活性，降低了 ROS 和脂质过氧化水平，从而减少了斑马鱼幼虫的细胞死亡。化合物 BP 和 EP 还通过稳定谷胱甘肽相关基因表达改善了谷胱甘肽氧化还原循环。
含羟基的化合物 BP 和 EP 是与氧化应激相关的病理状况的有前途的先导分子，它们通过增强谷胱甘肽氧化还原循环和酶抗氧化剂，对丙烯酰胺诱导的斑马鱼幼虫氧化应激表现出减弱作用。
