# New Achievements for the Treatment of Triple-Negative Breast Cancer
## 3 Novel Approaches to Therapy in TNBC
### Synthetic Compounds with Antiproliferative Activity in Preclinical Studies
#### 3.2.1 Carbazoles Derivatives or Biososters  
Recent advances in the scientific literature regarding TNBC antitumor activity of molecules with a carbazolic core have been extensively carried out [94]. Structures are reported in Table 2. Listing them, _N,N,N_-trimethylethanammonium iodide alkylcar-bazole **3** showed activity against MDA-MB-231 cell lines, and this activity was demonstrated to be strictly connected to the observed inhibition of human topoisomerase II (hTopo II) [95]. Moreover, the same research group studied the anticancer activity of four 1,4-dimethylcarbazole derivatives, analogues of a known antitumoral compound, ellipticine [96]. Particularly, compounds **4** and **5** possessed good anticancer activity on different BC cells, including triple-negative MDA-MB-231. This activity seems to be linked to their ability to inhibit DNA topoisomerase II. A study on 3-(alkyl(dialkyl))amino)benzoth[2,3-  
\begin{table}
\begin{tabular}{c c c c c} \hline \hline  & **Structure** & **Name** & **Original Indication** & **Ref** \\ \hline Na & & & & \\ \(\mathrm{OH}\) & & & & \\ \(\mathrm{OH}\) & & & & \\ \(\mathrm{OH}\) & & & & \\ \(\mathrm{OH}\) & & & & \\ \(\mathrm{OH}\) & & & & \\ \(\mathrm{OH}\) & & & & \\ \(\mathrm{N}\) & & & & \\ \(\mathrm{Cl}\) & & & & \\ \(\mathrm{Cl}\) & & & & \\ \(\mathrm{OH}\) & & & & \\ \(\mathrm{OH}\) & & & & \\ \hline \hline \end{tabular}
\end{table}
Table 1: Cont.  
\(f\)]quinazolin-1(2\(H\)) showed that compounds **6** and **7** exhibited good antitumor activity against MDA-MB-231 cell lines without cytotoxicity against normal cells. The compounds were suggested as multi-target tools due to their dual inhibition of different cellular proteins, e.g., tubulin and human topoisomerase I, involved in relevant cellular processes [97]. Interestingly, a nitrocarbazole acting against triple-negative MDA-MB-231 cell lines was recently proposed as a new microtubule-targeting agent in BC treatment [98,99]. Other research groups studied carbazole derivatives as anti-cancer and anti-migratory agents. In the study by [PERSON] et al. (2018) [100], compounds **8** and **9** inhibited the migration of metastatic cell line MDA-MB-231 by 32% and 34%, respectively, at 10 \(\upmu\)M, comparable with parent compound EHop-016, which exhibited anti-migratory activity of 33% at 10 \(\upmu\)M (and 17% at 5 \(\upmu\)M), but they did not inhibit the growth of the cell lines tested at concentrations \(\leq\) 50 \(\upmu\)M. On the other hand, compounds **10** and **11** inhibited the growth at \(\sim\)15 \(\upmu\)M but did not significantly inhibit migration. [PERSON] et al. (2014) [101] demonstrated that compound **12**, a carbazole derived with fluorophore, strongly induced apoptosis in vitro in a wide number of TNBC cancer cell lines. Moreover, it reduced the growth of human TNBC xenograft tumors (SUM149) in vivo without inducing severe toxicity. Both in vitro and in vivo studies showed that phospho-STAT3 inhibition was due to protein-tyrosine phosphatase PTPN6 upregulation. [PERSON] et al. (2018) [102] examined new derivatives of racemosin B, a natural indole[3,2-\(a\)]carbazole isolated from the green alga _Caulerpa racemose_. Among several alkyl-lamide derivatives, compound **13** exhibited good growth inhibition against human BC cell lines, inducing G2/M cell cycle arrest and apoptosis in MDA-MB-231 cancer cell lines.  
\begin{table}
\begin{tabular}{c c c} \hline \hline
**Structure** & **Compound** & **Ref** \\ \hline Cl & & **3** & [95]