Department of Chemistry (Inorganic Section), Jadavpur University, Kolkata 700 032, India; Department of Chemistry, Vijaygarh Jyotish Ray College, Kolkata 700 032, India.
Cancer Biology & Inflammatory Disorder Division, Indian Institute of Chemical Biology, Kolkata 700 032, India; Infectious Diseases and Immunology Division, Indian Institute of Chemical Biology, Kolkata 700 032, India.
J Inorg Biochem. 2023 Dec;249:112369. doi: 10.1016/j.jinorgbio.2023.112369. Epub 2023 Sep 21.
Quinalizarin, an analogue of anthracycline anticancer agents, is an anticancer agent itself. A Cu complex was prepared and characterized by elemental analysis, UV-Vis & IR spectroscopy, mass spectrometry, EPR and DFT. The intention behind the preparation of the complex was to increase cellular uptake, compare its binding with DNA against that of quinalizarin, modulation of semiquinone formation, realization of human DNA topoisomerase I & human DNA topoisomerase II inhibition and observation of anticancer activity. While the first two attributes of complex formation lead to increased efficacy, decrease in semiquinone generation could results in a compromise with efficacy. Inhibition of human DNA topoisomerase makes up this envisaged compromise in free radical activity since the complex shows remarkable ability to disrupt activities of human DNA topoisomerase I and II. The complex unlike quinalizarin, does not catalyze flow of electrons from NADH to O to the extent known for quinalizarin. Hence, decrease in semiquinone or superoxide radical anion could make modified quinalizarin [as Cu complex] less efficient in free radical pathway. However, it would be less cardiotoxic and that would be advantageous to qualify it as a better anticancer agent. Although binding to calf thymus DNA was comparable to quinalizarin, it was weaker than anthracyclines. Low cost of quinalizarin could justify consideration as a substitute for anthracyclines but the study revealed IC of quinalizarin/Cu-quinalizarin was much higher than anthracyclines or their complexes. Even then, there is a possibility that Cu-quinalizarin could be an improved and less costly form of quinalizarin as anticancer agent.
吖啶醌是一种蒽环类抗癌药物的类似物，本身也是一种抗癌药物。我们合成了一种铜配合物，并通过元素分析、紫外可见和红外光谱、质谱、电子顺磁共振和密度泛函理论对其进行了表征。合成该配合物的目的是增加细胞摄取，比较其与吖啶醌与 DNA 的结合，调节半醌的形成，实现人源拓扑异构酶 I 和人源拓扑异构酶 II 的抑制，并观察其抗癌活性。虽然配合物形成的前两个属性导致了疗效的提高，但半醌生成的减少可能会导致疗效的妥协。人源拓扑异构酶的抑制构成了这种预期的自由基活性的妥协，因为该配合物显示出显著的破坏人源拓扑异构酶 I 和 II 的活性的能力。与吖啶醌不同，该配合物不会像吖啶醌那样催化从 NADH 到 O 的电子流动，因此，半醌或超氧阴离子自由基的减少可能会使修饰的吖啶醌（如 Cu 配合物）在自由基途径中效率降低。然而，它的心脏毒性较小，这将使其成为一种更好的抗癌药物。虽然与小牛胸腺 DNA 的结合与吖啶醌相当，但比蒽环类药物弱。吖啶醌的低成本可以证明它可以替代蒽环类药物，但研究表明吖啶醌/Cu-吖啶醌的 IC 比蒽环类药物或它们的配合物高得多。即使如此，Cu-吖啶醌仍有可能成为一种改进的、成本更低的吖啶醌抗癌药物。
