Astrain-Redin Nora, Raza Asif, Encío Ignacio, Sharma Arun K, Plano Daniel, Sanmartín Carmen
Departamento de Tecnología y Química Farmacéuticas, Universidad de Navarra, Irunlarrea 1, 31008 Pamplona, Spain.
Department of Pharmacology, Penn State Cancer Institute, CH72, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Antioxidants (Basel). 2023 Jun 23;12(7):1331. doi: 10.3390/antiox12071331.
Oxidative stress surrounding cancer cells provides them with certain growth and survival advantages necessary for disease progression. In this context, Se-containing molecules have gained attention due to their anticancer and antioxidant activity. In our previous work, we synthesized a library of 39 selenoesters containing functional groups commonly present in natural products (NP), which showed potent anticancer activity, but did not demonstrate high radical scavenger activity. Thus, 20 novel Se derivatives resembling NP have been synthesized presenting acylselenourea functionality in their structures. Radical scavenger activity was tested using DPPH assay and in vitro protective effects against ROS-induced cell death caused by HO. Additionally, antiproliferative activity was evaluated in prostate, colon, lung, and breast cancer cell lines, along with their ability to induce apoptosis. Compounds and showed potent cytotoxicity against the tested cancer cell lines, along with high selectivity indexes and induction of caspase-mediated apoptosis. These compounds exhibited potent and concentration-dependent radical scavenging activity achieving DPPH inhibition similar to ascorbic acid and trolox. To conclude, we have demonstrated that the introduction of Se in the form of acylselenourea into small molecules provides strong radical scavengers in vitro and antiproliferative activity, which may lead to the development of promising dual compounds.
癌细胞周围的氧化应激为它们提供了疾病进展所需的某些生长和生存优势。在这种情况下,含硒分子因其抗癌和抗氧化活性而受到关注。在我们之前的工作中,我们合成了一个包含39种含有天然产物(NP)中常见官能团的硒酯库,这些硒酯显示出强大的抗癌活性,但没有表现出高自由基清除活性。因此,已经合成了20种类似NP的新型硒衍生物,其结构中具有酰基硒脲官能团。使用DPPH测定法测试自由基清除活性,并测试其对HO引起的ROS诱导的细胞死亡的体外保护作用。此外,还评估了其在前列腺癌、结肠癌、肺癌和乳腺癌细胞系中的抗增殖活性及其诱导凋亡的能力。化合物 和 对测试的癌细胞系显示出强大的细胞毒性,同时具有高选择性指数并诱导半胱天冬酶介导的凋亡。这些化合物表现出强大的、浓度依赖性的自由基清除活性,实现了与抗坏血酸和托洛克斯相似的DPPH抑制。总之,我们已经证明,以酰基硒脲形式将硒引入小分子中可提供强大的体外自由基清除剂和抗增殖活性,这可能会导致开发出有前景的双重作用化合物。