# Schiff Bases: Interesting Scaffolds with Promising Antitumoral Properties
## 2 Schiff Bases as Antiproliferative Agents
### Bis-Schiff Bases  
[PERSON] et al. (2001) [80] reported a study on 10 Schiff bases and evaluated their antiproliferative activity by measuring their effect on the (PG) of 57 different cancer cell lines, including lung, colon, central nervous system (CNS), ovarian, renal, prostate, melanoma, leukemia, and breast cancer. Compounds **59-62** (Table 2) showed activity against different cell lines. Particularly, compounds **59** and **60** were effective on leukemia (SR and MOLT-4) and colon (COLO-205), compound **62** on leukemia (SR and MOLT-4), CNS (SF-539) and melanoma (SK-MEL-28 and UACC-257). Against some of the abovementioned cell lines, other compounds have also been reported to be active, particularly, compound **61** on CNS, melanoma, and breast and compound **59** on leukemia, colon, and breast. Compound **60** was the most effective of mines analogues on leukemia. [PERSON] et al. (2009) [81] studied several Schiff bases and copper complexes as proteasome inhibitors and apoptosis inducers in human colon cancer HCT-116 cells, in comparison to curcumin. Among the synthesized compounds, the authors demonstrated that the fluorine-substituted curcumin analogs were superior to the curcumin against HCT-116 and BxPC-3 pancreatic cancer cells, probably because of the higher metabolic stability allowed by the fluoro substituents. Compound **63** showed approximately 80%, 60%, and 60% proteasome inhibition at 10, 20, and 30 \(\upmu\)M (curcumin: 27%, 47%, and 64% at 10, 20, and 30 \(\upmu\)M, respectively). In the study by [PERSON] et al. (2012) [56], described in the paragraph below, the activity of mono-Schiff bases and bis-Schiff bases was evaluated. Compound **64** showed activity against ovary (PA1) cancer cells (62% versus 93% of actinomycin-D) and **65** against both breast (T47D) and ovary (PA1) (41% and 53%, respectively, versus 21% and 93% of actinomycin-D, respectively) cancer cells.  
[PERSON] et al. (2020) [82] recently studied four tetrahydroobenzothiazzole-based Schiff bases and tested their cytotoxic activity against the human breast cancer (MCF-7) and hepatocellular liver carcinoma (HepG2) cell lines by MTT assay. The compounds showed cytotoxic activity against both cell lines in a concentration-dependent manner. Compound **66** was the most active against MCF-7 (IC\({}_{50}\) = 7.75 and 34.52 \(\upmu\)M, at 24 and 48 h, respectively) and HepG2 (IC\({}_{50}\) = 3.01 and 1.29 \(\upmu\)M, at 24 and 48 h, respectively). [PERSON] et al. (2021) [83] recently reported some selected bis-Schiff bases studied for their in vitro antiproliferative activity toward three human carcinoma HepG2 (liver), MCF-7 (breast), and RPE-1 (normal retina pigmented epithelium) cell lines using MTT assay. The results showed that compound **67** was found to be the active candidate against HepG2 (IC\({}_{50}\) = 84.2 \(\upmu\)M versus 25.3 \(\upmu\)M of doxorubicin) and MCF-7 cells (IC\({}_{50}\) = 99.4 \(\upmu\)M versus 20.9 \(\upmu\)M of doxorubicin), while compound **68** was found to be the most active of the series against RPE-1 cells (IC\({}_{50}\) = 127.7 \(\upmu\)M versus 19.1 \(\upmu\)M of doxorubicin).  
\begin{table}
\begin{tabular}{c c c} \hline \hline \(\upmu\)M & \(\upmu\)M & \(\upmu\)M \\ \hline \(\upmu\)M & \(\upmu\)M &  
\begin{table}
\begin{tabular}{c c} \hline \hline \
\begin{tabular}{c} effective on leukemia (SR and \\ MOLT-4), colon (COLO-205) and \\ breast. IC\({}_{50}\) values not reported. \\ \end{tabular} & [PERSON] et al., 2001 [80] \\ \end{tabular} \\ \hline
\begin{tabular}{c} effective on leukemia (SR and \\ MOLT-4), colon (COLO-205) and \\ leukemia. IC\({}_{50}\) values not reported. \\ \end{tabular} & [PERSON] et al., 2001 [80] \\ \end{tabular}
\end{table}
Table 2: Bis-Schiff bases.