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.
Keywords: 2-Azetidinone; Anthraquinone; Anticancer activity; Molecular docking; β-Lactam.
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