Anticancer activity and evaluation of apoptotic genes expression of 2-azetidinones containing anthraquinone moiety
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ORIGINAL ARTICLE
Anticancer activity and evaluation of apoptotic genes expression of 2‑azetidinones containing anthraquinone moiety Masoud Mohamadzadeh1 · Maaroof Zarei1,2 Received: 14 July 2020 / Accepted: 5 September 2020 © Springer Nature Switzerland AG 2020
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.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11030-020-10142-x) contains supplementary material, which is available to authorized users. * Maaroof Zarei [email protected]; [email protected] 1
Department of Biochemistry, Shiraz Branch, Islamic Azad University, Shiraz, Iran
Department of Chemistry, Faculty of Sciences, University of Hormozgan, Bandar Abbas 71961, Iran
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Molecular Diversity
Graphic abstract
Keywords β-Lactam · 2-Azetidinone · Anticancer activity · Anthraquinone · Molecular docking
Introduction 2-Azetidinones (β-lactams) are well-known as antibacterial compounds and β-lactam antibiotics have more market share than any other antibiotics [1]. β-Lactam antibiotics including penicillins, cephalosporins, carbapenems, clavulanic acid, sulbactams, tazobactams, nocardicins, and monobactams exert antimicrobial activity by means of interfering with enzymes that have specific correlation to peptidoglycan metabolism and induce damage to the cell wall [2]. Today, β-lactam derivatives are showing a wide range and specific biological activities [3–6]. Ezetimibe, the recent drug containing 2-azetidinone ring selectively inhibits intestinal cholesterol absorption [7]. In addition, 2-azetidinones display anticancer activity [8–10]. Furthermore, the selective b
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