Abstract Lead as a potent environmental and occupational pollutant, exerts its toxic effect mainly through oxidative stress induction. Currently, chelation therapy is the only medical management of metal intoxications in clinic, but its administration is associated with various side effects as well. In this study the protective effect of synthetized Piroxicam derivative was evaluated against lead toxicity in vitro. First the chelating activity of Piroxicam derivative was studied through Jobs method and 13C{1H} NMR spectroscopy. Then the cytoprotective effect of Piroxicam derivative (10, 20, 50, 100 and 200 μg/mL) was evaluated and compared with that of EDTA (30 μg/mL) in the presence of lead nitrate (30 μg/mL). The EC50 value of Piroxicam derivative was calculated as well. Finally, the chelation efficacy and antioxidant effects of Piroxicam derivative in EC50 and 2EC50 values was assessed and compared with that of EDTA. Results showed that Piroxicam derivative chelates lead ion as much as EDTA. Moreover, Piroxicam derivative prevented lead-induced cells death more effectively than EDTA which is may due to its potent innate antioxidant activity. In conclusion, the synthetized Piroxicam derivative with possessing potent chelating activity as well as potent antioxidant activity, could be considered as potential drug target in management of toxic metals poisoning.

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作为铅螯合剂的吡罗昔康衍生物的合成和生物学评价

摘要 铅作为一种强效的环境和职业污染物，主要通过氧化应激诱导发挥其毒性作用。目前，螯合疗法是临床上唯一的金属中毒药物治疗，但其给药也伴随着各种副作用。在这项研究中，评估了合成的吡罗昔康衍生物对体外铅毒性的保护作用。首先通过乔布斯法和13C{1H}核磁共振波谱研究吡罗昔康衍生物的螯合活性。然后评估吡罗昔康衍生物（10、20、50、100 和 200 μg/mL）的细胞保护作用，并在硝酸铅 (30 μg/mL) 存在下与 EDTA (30 μg/mL) 进行比较。还计算了吡罗昔康衍生物的 EC50 值。最后，评估了吡罗昔康衍生物在 EC50 和 2EC50 值中的螯合功效和抗氧化作用，并与 EDTA 进行了比较。结果表明，吡罗昔康衍生物与 EDTA 一样螯合铅离子。此外，吡罗昔康衍生物比 EDTA 更有效地防止了铅诱导的细胞死亡，这可能是由于其强大的先天抗氧化活性。综上所述，合成的吡罗昔康衍生物具有强螯合活性和抗氧化活性，可作为治疗有毒金属中毒的潜在药物靶点。吡罗昔康衍生物比 EDTA 更有效地防止铅诱导的细胞死亡，这可能是由于其强大的先天抗氧化活性。综上所述，合成的吡罗昔康衍生物具有强螯合活性和抗氧化活性，可作为治疗有毒金属中毒的潜在药物靶点。吡罗昔康衍生物比 EDTA 更有效地防止铅诱导的细胞死亡，这可能是由于其强大的先天抗氧化活性。综上所述，合成的吡罗昔康衍生物具有强螯合活性和抗氧化活性，可作为治疗有毒金属中毒的潜在药物靶点。