# Schiff Bases: Interesting Scaffolds with Promising Antitumoral Properties
## 2 Schiff Bases as Antiproliferative Agents
### Mono-Schiff Bases
Compound **27** was the only compound to show slight activity against liver HepG2 (IC\({}_{50}\) = 6.20 ug/mL) and breast MCF-7 (IC\({}_{50}\) = 7 ug/mL) cells in comparison with the standard drug, doxorubicin (IC\({}_{50}\) = 4.20 and 4.70 ug/mL, respectively). [PERSON] et al. (2013) [60] studied a series of Schiff bases and evaluated the in vitro antiproliferative activities against human breast cancer cell MCF-7 and mouse lymphocyte leukemia cell L1210 by the WST-8 ([2-(2-methoxy-4-nitrophenyl)-3(4-nitrophenyl)-5-(2,4-disulophenyl)-2H-tetrazol-monosodium salt]) assay as a substitute for the most classic MTT assay. The lead compound 2-phenyl-4-carboxyl-1,3-selenazole (PCS) was taken as a comparison. Compounds **28-30** were the most potent compounds against MCF-7 (IC\({}_{50}\) = 4.02, 7.55 and 8.51 uM, respectively, versus 16.56 uM of PCS). Compound **31** was the most active against L1210 (IC\({}_{50}\) = 38.73 uM versus 60.11 uM of PCS). [PERSON] et al. (2013) [61] reported a study on Schiff bases and evaluation of their antioxidant, antitumor, and anti-inflammatory potentials. The antitumor activity was assessed by the potato disc anti-tumor assay. Compounds **32** and **33** were the most active, showing IC\({}_{50}\) values of 0.15 and 8.03 ug/mL, respectively, versus 0.003 ug/mL of vincristine, used as reference drug. [PERSON] et al. (2014) [62] synthesized a series of Schiff bases and evaluated the in vitro antitumor activity against three human tumor cell lines (human liver SMMC-7721, human breast MCF-7, and human lung A549) using the WST-8 assay and 5-Fluorouracil (5-FU) as a positive control. Compound **34** was the most active against SMMC-7721 cells (IC\({}_{50}\) = 2.84 uM versus 5-FU, IC\({}_{50}\) = 5.62 uM), whereas compounds **35** and **36** showed significant antiproliferative activity against MCF-7 cells (IC\({}_{50}\) = 4.56 and 4.25 uM, respectively, versus 14.26 uM of 5-FU). Finally, the most interesting compounds against A549 cells were **37** and **36** (IC\({}_{50}\) = 4.11 and 4.13 uM, respectively, versus 8.13 uM of 5-FU). [PERSON] et al. (2015) [63] synthesized 13 Schiff bases and studied their potential as Hsp 90 ATPase inhibitors by malachite green assay and antiproliferative activity against PC3 prostate cancer cell lines by MTT assay. Compound **38** showed a high effect toward PC3 cells with an IC\({}_{50}\) of 4.83 uM (versus 2.45 uM of geldanamycin), followed by compounds **39** and **40** (IC\({}_{50}\) = 7.43 uM and 7.15 uM, respectively), which were the other promising anti-cancer molecules among the newly synthesized compounds. In malachite green assay for Hsp90 ATPase suppression, none of the molecules demonstrated IC\({}_{50}\) values in nanomolar range. Only compounds **41** and **42** showed the maximum inhibitory potential, with an IC\({}_{50}\) value of 0.02 uM. In conclusion, the authors identified the compound **38**, showing sub micro-molar target affinity and good cellular potency, as the lead molecule for preclinical evaluation in animals and development of Hsp90 inhibitors as anticancer agents. [PERSON] et al. (2016) [64] synthesized and studied a Schiff base ligand (**43**) and its complexes with metal ions. Compound **43** was tested for its anticancer activity against different human tumor cell lines (liver HepG2, breast MCF-7, and colorectal HCT116) and doxorubicin was used as a reference drug. It showed IC\({}_{50}\) = 9.22, 10.00, and 9.50 uM against the tree cell lines, respectively (IC\({}_{50}\) values for doxorubicin were 4.20, 4.40, and 5.25 uM, respectively). [PERSON] et al. (2018) [65] described the design, synthesis, and biological evaluation of new phenylimino-1,2-diphenylethanol derivatives in human colon carcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines.