## 2 Antiproliferative Activity of Schiff Bases Complexed with Transition Metals  
Complexes of Schiff bases with transition metals are summarized in Table 1. Several complexes of Schiff bases with Cu(II), Co(II) and Ni(II) were studied as antitumor agents against colorectal adenocarcinoma (HT29) cells by [PERSON] et al. (2017) [43]. The Co(II) complex **1** showed higher anticancer activity than its corresponding ligand, particularly being able to inhibit cancer cells growth of about the 83.22% after 72 h, as determined by 3-(4,5-dimethylthiazol-2-yl), 2,5-diphenyltrazolium bromide (MTT) assay. [PERSON] et al. (2019) [44] studied Schiff base complexes of Co(II) and Ni(II) ions with diethyl 3,3'-(ethane-1,2-diylbis(azancyylidene))(3E,3'E)-dibutyrate (H\({}_{2}\)L\({}^{1}\)) and (3E,3'E)-3,3'-(ethane-1,2-diylbis (azanylylidene))bis(N-(pyrididin-2-yl))butanamide) (H\({}_{2}\)L\({}^{2}\)) as ligands, and studied their antimicrobial and antiproliferative activity. [Ni\({}_{2}\)(L\({}^{1}\))Cl\({}_{2}\)\(\cdot\)6H\({}_{2}\)O]\({}_{2}\)H\({}_{2}\)O (2) and [Co\({}_{2}\)(H\({}_{2}\)L\({}^{2}\))Cl\({}_{4}\)\(\cdot\)2H\({}_{2}\)O]\({}_{2}\)H\({}_{2}\)O (3) showed antiproliferative activity against the MCF-7 cell line (IC\({}_{50}\) = 27.21 and 13.89 uM, respectively, versus IC\({}_{50}\) = 4.17 uM of doxorubicin). [PERSON] et al. (2020) [45] studied five transition metal complexes TM\({}_{3}\)L\({}_{2}\)(OAc)\({}_{2}\) (TM = transition metal) with the \(N\),\(N^{\prime}\)-bis([(2-hydroxy-1-naphthalenyl)methylene]-propane-1,3-diamine, which is a bis-Schiff base, and determined the in vitro anticancer activities against seven human cancer cell lines (namely, gastric cancer MGC80-3, HeLa, human bladder T-24, HepG2, MDA, A549, human hepatocellular carcinoma Bel-7402 and human lung Wi-38 cancer cell lines), by the MTT assay. The complexes with Cu, Ni and Fe **(4-6)** showed higher antitumor activities than cisplatin and the highest inhibitory effects were found for complex **4** (IC\({}_{50}\) lower than 0.5 uM for human bladder cancer cell line T-24) while showing nearly no toxicity to the normal cell HL-7702 as revealed by flow cytometry. The complex **4** induced tumor cell apoptosis by reducing the Bcl-2/Bax ratio, blocking the T-24 tumor cells at the G2/M phase, reducing the mitochondrial membrane potential, increasing the intracellular concentration of reactive oxygen species (ROS) and Ca\({}^{2+}\), and changing protein expression. The apoptosis induced by complex **4** has been found to be triggered by Caspases 3/8 activation in T24 cells. [PERSON] et al. (2020) [46] synthesized the metal complexes of a tridentate Schiff base ligand (\(E\))-1-(2-hydroxy-3-methoxyenylidene)-3-phenylurea with Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and Zr(IV) (7-9 are shown in Table 1). The ligand and its metal complexes were screened for their cytotoxic activity against two cell lines, i.e., human colon carcinoma (HCT-116) and breast carcinoma cells (MCF-7), using cisplatin as standard drug and obtaining IC\({}_{50}\) values of 7.22 \(\upmu\)g/mL and 6.9 \(\upmu\)g/mL against MCF-7 and HCT-116, respectively. All the complexes were more active than the free Schiff base ligand and, in particular, the higher cytotoxic activity was exerted by Cu, Co and Zn complexes (IC\({}_{50}\) = 61.1, 90.4 and 61.3 \(\upmu\)g/mL on MCF-7 cells, respectively; IC\({}_{50}\) = 52.7, 60.6 and 51.9 \(\upmu\)g/mL on HCT-116, respectively). [PERSON] et al. (2020) [47] studied a Cu(II)-Mn(II) Schiff base tetradentate complex alone or in combination with cisplatin against squamous cell carcinoma cell line (SCC) in vitro, adopting the oral-derived gingival mesenchymal stem cells (GMSCs) as control. The IC\({}_{50}\) values, obtained via MTT assay, were 1 \(\upmu\)g/mL for cisplatin and 250 \(\upmu\)M for the Schiff base complex [Cu(1-(biphenyl)-2-hydroxyimino-2-(4-chloroanilino)-1-ethanoneone)(H\({}_{2}\)O)Mn(phen)\({}_{2}\)(ClO\({}_{4}\))\({}_{2}\) (**10**) on both the cell lines.