Reimann Hauke, Ngo Quoc Anh, Stopper Helga, Hintzsche Henning
Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Straße 9, 97078 Würzburg, Germany.
Institute of Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, CauGiay, Hanoi, Viet Nam.
Toxicol Rep. 2020 Nov 20;7:1588-1591. doi: 10.1016/j.toxrep.2020.11.004. eCollection 2020.
Celecoxib is used widely for the acute treatment of pain and for pain relief in various diseases. Furthermore, it shows potential in chemoprevention, although chronic treatment with celecoxib could lead to adverse effects like cardiovascular events. New derivatives of celecoxib were synthesised that may be suitable as chemopreventive agent without inducing adverse effects. Critical endpoint for a safe use of pharmaceuticals is genotoxicity after application. A standard test for the assessment of genotoxicity is the cytokinesis-block micronucleus assay, that evaluates the number micronuclei after treatment of cells with a test compound as biomarker for DNA damage. Various promising derivatives of celecoxib have been assessed with the cytokinesis-block micronucleus assay in HeLa-H2B-GFP cells. It could be demonstrated, that neither celecoxib nor its derivatives were genotoxic in this assay and therefore celecoxib derivatives could be developed further for a safe use as chemopreventive agent.
塞来昔布被广泛用于疼痛的急性治疗以及各种疾病的止痛。此外,它在化学预防方面显示出潜力,尽管长期使用塞来昔布可能会导致心血管事件等不良反应。合成了塞来昔布的新衍生物,这些衍生物可能适合作为化学预防剂而不引起不良反应。药物安全使用的关键终点是用药后的遗传毒性。评估遗传毒性的标准测试是胞质分裂阻断微核试验,该试验通过用测试化合物处理细胞后评估微核数量,以此作为DNA损伤的生物标志物。已在HeLa-H2B-GFP细胞中用胞质分裂阻断微核试验评估了塞来昔布的各种有前景的衍生物。结果表明,在该试验中塞来昔布及其衍生物均无遗传毒性,因此塞来昔布衍生物可进一步开发以安全用作化学预防剂。