Ceramella Jessica, Rosano Camillo, Iacopetta Domenico, Ben Toumia Iméne, Chekir-Ghedira Leila, Maatouk Mouna, Mariconda Annaluisa, Longo Pasquale, Dallemagne Patrick, Rochais Christophe, Sinicropi Maria Stefania
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via Pietro Bucci, 87036 Arcavacata di Rende, Italy.
U.O. Proteomica e Spettrometria di Massa, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi, 10, 16132 Genova, Italy.
Pharmaceutics. 2025 Mar 25;17(4):415. doi: 10.3390/pharmaceutics17040415.
Carbazoles represent one of the most important classes of nitrogen-based tricyclic aromatic heterocycles and are present in natural sources and chemically obtained drugs. Recently, several research groups disclosed their large biological and chemical applications in different fields, leading to an increased interest towards this class of molecules. Some of the obtained derivatives have been successfully employed in the clinical treatment of different tumor types, but the onset of heavy side effects impaired their efficacy and discouraged their use. Pursuing the aim of obtaining carbazoles with less negative features, a lot of chemically modified compounds have been produced and evaluated. : In this paper, we describe the in vitro and in vivo evaluation of a bis-carbazole derivative with strong anticancer properties against two breast cancer cell lines. : This compound has been found to impact the cell cytoskeleton dynamics, triggering the activation of some key proteins playing a role in the intrinsic and extrinsic apoptotic pathways. Equally important, this derivative has been found to be selective for cancer cells and has shown a safe profile in Balb/c-treated mice. : Overall, the disclosed outcomes represent an important landmark for encouraging further studies directed toward the potentiation of this lead to be potentially exploited in both preclinical and clinical applications.
咔唑是最重要的一类含氮三环芳香杂环化合物之一，存在于天然来源以及化学合成药物中。最近，几个研究小组揭示了它们在不同领域的广泛生物学和化学应用，这引发了人们对这类分子的更多关注。一些得到的衍生物已成功用于不同类型肿瘤的临床治疗，但严重副作用的出现影响了它们的疗效并阻碍了其应用。为了获得具有较少负面特性的咔唑，人们制备并评估了许多化学修饰的化合物。在本文中，我们描述了一种对两种乳腺癌细胞系具有强大抗癌特性的双咔唑衍生物的体外和体内评估。已发现该化合物影响细胞骨架动力学，触发一些在内在和外在凋亡途径中起作用的关键蛋白的激活。同样重要的是，已发现该衍生物对癌细胞具有选择性，并且在经其处理的Balb/c小鼠中显示出安全的特性。总体而言，所披露的结果是一个重要的里程碑，有助于鼓励进一步开展研究，以增强这种先导化合物的活性，使其有可能在临床前和临床应用中得到利用。
