# Schiff Bases: Interesting Scaffolds with Promising Antitumoral Properties
## 2 Schiff Bases as Antiproliferative Agents
### Mono-Schiff Bases
(2012) [54] synthesized two anthracene-containing Schiff bases, 9-anthrylidene-p-toluidine (**20**) and 9-anthrylidene-furfurylamine (**21**), and tested their anticancer activities in vitro on a panel of human epithelial cancer cell lines (cell lines from ductal carcinoma of the breast with low and high metastatic potential, MCF-7 and MDA-MB-231, respectively; colostrum-derived myoepithelial cells, expressing polyoma virus large T-antigen, HBL-100 line; bladder carcinoma, 647-V; hepatocellular carcinoma, HepG2;colon carcinoma, HT-29; cervical carcinoma, HeLa). Compounds **20** and **21** showed high cytotoxic activity toward colon carcinoma HT-29 cell line (IC\({}_{50}\) = 0.08 and 0.20 mg/mL versus 0.58 mg/mL of doxorubicin). The authors also performed their safety testing, both in vitro (Neutral Red Uptake Assay, 3T3 NRU test) and _in vivo_ on ICR mice for genotoxicity and antiproliferative activity. Both compounds were shown not to induce clearly expressed dose-effect clasogenic activities, in contrast to the alkylating agent Mitomycin C. [PERSON] et al. (2012) [55] synthesized new Schiff bases and evaluated their anti-melanogenesis activity, in murine B16F10 melanoma cells, through the inhibition of tyrosinase. Compound **12** exhibited the most potent and non-competitive inhibition on mushroom tyrosinase, even better than the kojic acid used as positive reference (IC\({}_{50}\) value of 17.22 uM versus 51.11 uM of the kojic acid). This compound decreased the melanin production stimulated by the alpha-melanocyte-stimulating hormone and inhibited murine tyrosinase activity in a dose-dependent manner. [PERSON] et al. (2012) [56] synthesized several mono-Schiff bases and bis-Schiff bases and studied their anticancer activities against five human cancer cell lines (lung, NCI H-522; ovary, PA1; breast T47D; colon, HCT-15; liver, HepG2) by MTT assay. The percentage growth (PG) inhibition of cancer cell lines was determined at a concentration of 1 \(\times\) 10\({}^{-5}\) M. The most active mono-Schiff base against lung cancer cells (49% versus 59% of actinomycin-D) was compound **22**. The other active bis-Schiff bases are reported in the next paragraph. [PERSON] et al. (2013) [57] studied several small molecules bearing an imine moiety and studied their activity against four esophageal cancer cell lines. Compound **23** was the most active of the series, showing IC\({}_{50}\) values of 50.12, 158.49, and 111.2 uM against KYSE 150, KYSE 30 and KYSE 270. [PERSON] et al. (2013) [58] studied several Schiff bases as antiproliferative agents against various cell lines by using the MTT assay. The most interesting compounds, more active than standard drugs, were **24-26**. In particular, **24** was active on ovarian carcinoma (SK OV-3) cell line (IC\({}_{50}\) = 0.44 uM versus 4.16 uM of doxorubicin), whereas compound **25** showed good activity on leukemia (U937) (IC\({}_{50}\) = 0.09 nM versus 4.45 of doxorubicin), neuroblastoma (GOTO and NB-1) (IC\({}_{50}\) = 0.45 nM and 0.64 nM, respectively, versus IC\({}_{50}\) = 4.73 nM and IC\({}_{50}\) = 5.15 nM, respectively, of doxorubicin), and fibrosarcoma (HT1080) cell lines (IC\({}_{50}\) = 0.54 nM versus 1.16 nM of tamoxifen). Finally, compound **26** was active on cervical carcinoma (KB) (IC\({}_{50}\) = 0.54 uM versus 4.46 uM of fluorouracil), CNS (SF-268) (IC\({}_{50}\) = 0.30 nM versus 7.68 nM of cytarabine), leukemia (K-562) (IC\({}_{50}\) = 0.43 nM versus 6.66 of doxorubicin), liver (HepG2) (IC\({}_{50}\) = 0.09 nM versus 1.31 nM of tamoxifen), and non-small cell lung (NCI H460) cancer cell lines (IC\({}_{50}\) = 6.60 nM versus 2.13 nM of gemcitabine hydrochloride). [PERSON] et al. (2015) [59] synthesized several imines and evaluated their cytotoxicity against four human cancer cell lines (colon HCT-116, lung A549, breast MCF-7, and liver HepG2) according to Sulforhodamine-B stain (SRB) assay.