Abstract

Nowadays, one of the principal causes of death in the world is cancer. A series of 2-azetidinones containing anthraquinone moiety with various substituents were synthesized using [2 + 2] ketene-imine cycloaddition (Staudinger ketene-imine cycloaddition), and their cytotoxicity against some human cancer and normal cell lines was evaluated. Some of these hybrid compounds showed moderate to significant cytotoxicity against breast carcinoma (MCF7), colon carcinoma (HCT116), prostate carcinoma (PC3), and neuroblastoma (SKNMC) cell lines via MTT assay. Surprisingly, hybrid 4gh with the best anticancer activity demonstrated very good antibacterial and antifungal activities. This compound was selected to study to test on human fibroblast (Hu02) normal cell and comparison with doxorubicin. While 2-azetidinone 4gh represented similar cytotoxicity against cancer cell lines compared to doxorubicin, the 2-azetidinone demonstrated lower cytotoxicity against human fibroblast (Hu02) than doxorubicin. Further real-time PCR investigation displayed the expression of Bcl-xl, KI-67, TPX2 and BAX genes were significantly increased or decreased as desired in the cancer cell lines studied by treatment with doxorubicin or 2-azetidinone-anthraquinone 4gh. Molecular docking studies represented that hybrid 4gh strongly fitted the active site of topoisomerase II (PDB 4G0V) with hydrogen bond and hydrophobic interactions.

Graphic abstract

中文翻译：

---

含有蒽醌部分的 2-氮杂环丁酮的抗癌活性和凋亡基因表达的评价。

摘要

如今，世界上主要的死亡原因之一是癌症。使用[2 + 2] 烯酮-亚胺环加成（Staudinger ketene-imine cycloaddition）合成了一系列含有各种取代基的蒽醌部分的2-氮杂环丁酮，并评估了它们对一些人类癌症和正常细胞系的细胞毒性。通过 MTT 测定，其中一些杂合化合物对乳腺癌 (MCF7)、结肠癌 (HCT116)、前列腺癌 (PC3) 和神经母细胞瘤 (SKNMC) 细胞系显示出中度至显着的细胞毒性。令人惊讶的是，具有最佳抗癌活性的混合4gh表现出非常好的抗菌和抗真菌活性。选择该化合物进行研究以对人成纤维细胞（Hu02）正常细胞进行测试并与多柔比星进行比较。而 2-氮杂环丁酮与多柔比星相比， 4gh对癌细胞系具有相似的细胞毒性，2-氮杂环丁酮对人成纤维细胞 (Hu02) 的细胞毒性低于多柔比星。进一步的实时 PCR 研究显示 Bcl-xl、KI-67、TPX2 和 BAX 基因的表达在通过用阿霉素或 2-氮杂环丁酮-蒽醌4gh处理研究的癌细胞系中显着增加或减少。分子对接研究表明，混合4gh与拓扑异构酶 II (PDB 4G0V) 的活性位点具有氢键和疏水相互作用。

图形摘要