Abstract
Breast cancer is still considered a high-incidence disease, and numerous are the research efforts for the development of new useful and effective therapies. Among anticancer drugs, carbazole compounds are largely studied for their anticancer properties and their ability to interfere with specific targets, such as microtubule components. The latter are involved in vital cellular functions, and the perturbation of their dynamics leads to cell cycle arrest and subsequent apoptosis. In this context, we report the anticancer activity of a series of carbazole analogues 1–8. Among them, 2-nitrocarbazole 1 exhibited the best cytotoxic profile, showing good anticancer activity against two breast cancer cell lines, namely MCF-7 and MDA-MB-231, with IC50 values of 7 ± 1.0 and 11.6 ± 0.8 μM, respectively. Furthermore, compound 1 did not interfere with the growth of the normal cell line MCF-10A, contrarily to Ellipticine, a well-known carbazole derivative used as a reference molecule. Finally, in vitro immunofluorescence analysis and in silico studies allowed us to demonstrate the ability of compound 1 to interfere with tubulin organization, similarly to vinblastine: a feature that results in triggering MCF-7 cell death by apoptosis, as demonstrated using a TUNEL assay.
Highlights
Despite many research efforts, breast cancer incidence is constantly growing and remains a serious health emergency [1]
Breast cancers are classified according to specific subtypes defined by their histopathological features, and their expression of hormone receptors and growth factors, such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)
The most promising compound was 2-nitrocarbazole 1, which exerted good anticancer activity against both breast cancer cell lines used in this assay, with IC50 values of 7.0 ± 1.0 and 11.6 ± 0.8 μM on MCF-7 and MDA-MB-231, respectively
Summary
Breast cancer incidence is constantly growing and remains a serious health emergency [1]. The carbazole scaffold represents an important structural motif of many natural and/or syncarbazole scaffold represents an important structural motif of many natural and/or synthetic pharmacologically active compounds [6]. Against two human anticancer activity of a series of carbazole derivatives (1–8, Figure 1) against two human breast breast cancer cancer cell cell lines, lines, namely namely ER(+). The exhibited thethe best anticancer activity on on both the breast cancer cell lines used. Are anThese important starting in medicinal cancer treatment as a microtubule-targeting results are an point important starting chemistry for the development therapy to reduce theable numerous toxic point in medicinal chemistry for of thetargeted development of able targeted therapy to reduce the effects typically associated with traditional approaches.
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