In this research, betulin derivatives were bonded to the 1,4-quinone fragment by triazole linker. Furthermore, the enzymatic assay used has shown that these compounds are a good DT-diaphorase (NQO1) substrates as evidenced by increasing enzymatic conversion rates relative to that of streptonigrin. The anticancer activities of the hybrids were tested against a panel of human cell lines, like: melanoma, ovarian, breast, colon, and lung cancers. The structure-activity relationship showed that the activity depends on the type of 1,4-quinone moiety and the tumor cell lines used. It was also found that the anticancer effects were increasing against the cell line with higher NQO1 protein level, like: breast (T47D, MCF-7), colon (Caco-2), and lung (A549) cancers. The transcriptional activity of the gene encoding a proliferation marker (H3 histone), cell cycle regulators (p53 and p21) and apoptosis pathway (BCL-2 and BAX) for selected compounds were determined. The molecular docking study was carried out to examine the interaction between the hybrids and NQO1 enzyme. The computational simulation showed that the type of the 1,4-quinone moiety influences location of the compound in the active site of the enzyme. It is worth noting that the study of new hybrids of betulin as substrate for NQO1 protein may lead to new medical therapeutic applications in the future.

在这项研究中，桦木脑衍生物通过三唑接头与 1,4-醌片段结合。此外，所使用的酶促测定表明，这些化合物是良好的 DT-黄递酶 (NQO1) 底物，这可以通过相对于链黑素酶的酶促转化率增加来证明。针对一组人类细胞系测试了杂交体的抗癌活性，例如：黑色素瘤、卵巢癌、乳腺癌、结肠癌和肺癌。构效关系表明活性取决于 1,4-醌部分的类型和使用的肿瘤细胞系。还发现对 NQO1 蛋白水平较高的细胞系的抗癌作用正在增加，例如：乳腺癌（T47D、MCF-7）、结肠癌（Caco-2）和肺癌（A549）癌。编码增殖标记（H3组蛋白）的基因的转录活性，确定了所选化合物的细胞周期调节剂（p53 和 p21）和细胞凋亡途径（BCL-2 和 BAX）。进行分子对接研究以检查杂交体与 NQO1 酶之间的相互作用。计算模拟表明，1,4-醌部分的类型会影响化合物在酶活性位点中的位置。值得注意的是，以桦木脑为 NQO1 蛋白底物的新型杂交体的研究可能会在未来带来新的医学治疗应用。4-醌部分影响化合物在酶活性位点中的位置。值得注意的是，以桦木脑为 NQO1 蛋白底物的新型杂交体的研究可能会在未来带来新的医学治疗应用。4-醌部分影响化合物在酶活性位点中的位置。值得注意的是，以桦木脑为 NQO1 蛋白底物的新型杂交体的研究可能会在未来带来新的医学治疗应用。