# Schiff Bases: Interesting Scaffolds with Promising Antitumoral Properties
## 2 Schiff Bases as Antiproliferative Agents  
### Mono-Schiff Bases  
[PERSON] et al. (2003) [43] studied a series of Schiff bases and tested their antiproliferative activity against a panel of human cell lines derived from hematological and solid tumors. The most interesting compounds were **1-3** (Table 1). All of them inhibited the growth of leukemia cell lines, with IC\({}_{50}\) values ranging between 1.5 and 7 uM against human CD4\({}^{+}\) lymphocytes (MT-4), human CD4\({}^{+}\) acute T-lymphoblastic leukemia (CCRF-CEM), human splenic B-lymphoblastoid cells (WIL-2 NS), and human acute B-lymphoblastic leukemia (CCRF-SB). The 2-Amino-6-mercaptoethanol purine was used as reference drug (IC\({}_{50}\) between 0.1 and 0.5 uM). Particularly, compound **3** was also active against solid tumor-derived cell lines' skin melanoma and breast adenocarcinoma cells (IC\({}_{50}\) = 6 and 10 nM) against human skin melanoma SK-MEL-28 and human breast adenocarcinoma MCF-7 cell lines, respectively. The values for 2-amino-6-mercaptoethanol purine were 5 and 4 uM, respectively. [PERSON] et al. (2007) [44] studied several times bearing thiazole and triazole moieties and evaluated their antiproliferative activities against leukemia, stomach, and larynx cancer cell lines. The 2,4-dinitro substituted Schiff base **4** displayed high activity against HL-60, BGC-823 and Hep-2 cell lines, showing percentage inhibition of 91.97, 98.49, and 91.16%, respectively. [PERSON] et al. (2009) [45] studied several Schiff bases as derivatives of xanthotoxin and evaluated their antitumor activities against cervical carcinoma (HeLa) and breast carcinoma (MCF 7) cell lines. The Schiff base **5** was inactive against MCF-7 cell line but was the most interesting against HeLa, showing an IC\({}_{50}\) value of 7.2 uM and a percent viability of 70% (xanthotoxin, 7.6 uM and 62%, respectively). [PERSON] et al. (2009) [46] studied three Schiff bases and evaluated their antiproliferative activity, using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltratrazolium bromide (MTT) assay, against four human leukemic cell lines, viz., LAMA-84 (peripheral chronic myeloid leukemia cells), K-562 (non-adherent chronic myelogenous leukemia cells of the erythroleukemia type), HL-60 (acute promylocytic leukemia cells) and its multi-drug-resistant sub-line HL-60/Dox (multi-drug resistant acute myeloblastic leukemia cell line), characterized by the overexpression of MRP-1 protein (ABC-C1). Compound **6** showed antiproliferative activity (IC\({}_{50}\) = 39.9 uM, 29.9 uM, and 68.6 uM against LAMA-84, K-562, and HL-60/Dox, respectively), while compound **7** was less active (IC\({}_{50}\) = 251.9 uM, 212.9 uM, and 226.1 uM against LAMA-84, K-562, and HL-60/Dox, respectively). Both the investigated compounds were identified as capable of evoking the distinctly marked lower cytotoxic effects (with the IC\({}_{50}\) values over 400 uM) against the sensitive leukemic cell line HL-60 in a preliminary antitumor screening. [PERSON] et al. (2009) [47] studied Schiff bases with ferrocene addition and evaluated their antitumor, antioxidant, and DNA-protecting activities. Antitumor activity was eval  
Figure 1: General structure of a Schiff base. uated by Potato disc tumor induction assay using _Agrobacteriumium tunefaciens_ (At-10) to induce tumors on potato discs, that is, a prescreen assay and its results were in accordance with other commonly used in vitro antitumor assays. All the tested compounds inhibited tumor production for treatment of 1000, 100, and 10 \(\upmu\)g/mL concentration at \(p<0.05\) (vincristine, used as positive control, showed 100% tumor inhibition at all concentrations tested). The inhibition was observed in a dose-dependent manner with the highest inhibition at 1000 \(\upmu\)g/mL concentration. Moreover, the highest tumor growth inhibition of 71% was observed with ferrocene containing Schiff base **8**, followed by **9** with 58% inhibition at 1000 \(\upmu\)g/mL. IC\({}_{50}\) values were 20 and 563 \(\upmu\)g/mL versus 0.003 \(\upmu\)g/mL of vincristine.