Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Faculty of Sustainability, Leuphana University of Lüneburg, Scharnhorststraße 1/C13, DE-21335 Lüneburg, Germany; Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.
Sci Total Environ. 2013 Oct 1;463-464:140-50. doi: 10.1016/j.scitotenv.2013.05.082. Epub 2013 Jun 21.
Thalidomide (TD), besides being notorious for its teratogenicity, was shown to have immunomodulating and anti-inflammatory activities. This is why recently TD became a promising drug for the treatment of different cancers and inflammatory diseases. Yet nothing is known about the environmental fate of TD, which therefore was assessed experimentally and by in silico prediction programs (quantitative structure activity relationship (QSAR) models) within this study. Photolytic degradation was tested with two different light sources (medium-pressure mercury lamp; xenon lamp) and aerobic biodegradability was investigated with two OECD tests (Closed Bottle test (CBT), Manometric Respirometry test (MRT)). An additional CBT was performed for TD samples after 16 min of UV-photolysis. The primary elimination of TD was monitored and the structures of its photo-, abiotic and biodegradation products were elucidated by HPLC-UV-Fluorescence-MS(n). Furthermore, elimination of dissolved organic carbon was monitored in the photolysis experiment. LC-MS revealed that new photolytic transformation products (TPs) were identified, among them two isomers of TD with the same molecular mass. These TPs were different to the products formed by biodegradation. The experimental findings were compared with the results obtained from the in silico prediction programs where e.g. a good correlation for TD biodegradation in the CBT was confirmed. Moreover, some of the identified TPs were also structurally predicted by the MetaPC software. These results demonstrate that TD and its TPs are not readily biodegradable and not fully mineralized by photochemical treatment. They may therefore pose a risk to the aquatic environment due to the pharmacological activity of TD and unknown properties of its TPs. The applied techniques within this study emphasize the importance of QSAR models as a tool for estimating environmental risk assessments.
沙利度胺（TD）除了致畸性臭名昭著外，还具有免疫调节和抗炎活性。这就是为什么最近 TD 成为治疗不同癌症和炎症性疾病的有前途的药物。然而，对于 TD 的环境归宿知之甚少，因此本研究通过实验和计算机预测程序（定量构效关系（QSAR）模型）对其进行了评估。使用两种不同的光源（中压汞灯；氙灯）测试了光降解，并用两项 OECD 测试（密闭瓶测试（CBT）、测压呼吸计测试（MRT））研究了需氧生物降解性。在 UV 光解 16 分钟后，对 TD 样品进行了额外的 CBT。监测了 TD 的主要消除情况，并通过 HPLC-UV-荧光-MS(n) 阐明了其光解、非生物和生物降解产物的结构。此外，还监测了光解实验中溶解有机碳的消除情况。LC-MS 表明，鉴定出了新的光解转化产物（TP），其中包括两种具有相同分子量的 TD 异构体。这些 TPs 与生物降解形成的产物不同。实验结果与计算机预测程序的结果进行了比较，例如，在 CBT 中，TD 生物降解得到了很好的相关性。此外，一些鉴定出的 TPs 也被 MetaPC 软件结构预测。这些结果表明，TD 及其 TPs 不易生物降解，光化学处理也不能完全矿化。因此，由于 TD 的药理学活性和其 TPs 的未知特性，它们可能对水生环境构成风险。本研究中应用的技术强调了 QSAR 模型作为估计环境风险评估工具的重要性。
