## 3 Antiproliferative Activity of Schiff Bases Complexed with Platinum Group Metals (PGM)  
Platinum group metals are represented by Ru, Rh, Pd, Os, Ir and Pt and can be coordinated by Schiff base ligands as shown in Table 2. [PERSON] et al. (2017) [56] reported a study on palladium(II) and platinum(II) complexes based on pyrrole Schiff bases and their anticancer activity against various human cancerous (Caco-2, HeLa, HepG2, MCF-7, and PC-3) and noncancerous (MCF-12A) cell lines using MTT and apoptosis assays, respectively. The **29** complex showed an enhanced and selective cytotoxicity particularly against the HepG2 (IC\({}_{50}\) = 0.3 \(\upmu\)g/mL) and Caco-2 (IC\({}_{50}\) = 16.63 \(\upmu\)g/mL) cells. It reduced the viability of the five cancerous cell lines, which included one breast cancer cell line, by more than 60%. The **30** complex reduced the cell viability, in all types, by more than 80%. The IC\({}_{50}\) values were 13.0 and 15.81 \(\upmu\)g/mL against HepG2 and Caco-2 cells, respectively. Moreover, it also demonstrated a strong intercalation binding affinity for the CTDNA (binding constant \(K_{\text{b}}\) = 8.049 \(\times\) 10\({}^{4}\) M\({}^{-1}\)). [PERSON] et al. (2020) [57] synthesized a series of palladium(II) complexes of \(N\)-(5-nitro-salylidene)-Schiff bases (**31-33**, [Pd(L)(H\({}_{2}\)O)]\(\times\)H\({}_{2}\)O) and studied the in vitro cytotoxicity against tumor cell lines HeLa and MCF-7, and the normal human cell line HEK-293. The complexes **31** and **32** showed a moderate antitumor activity against HeLa cell lines, while **33** was the most active, showing higher activity than the standard anticancer drug, doxorubicin. All three complexes were more active than doxorubicin against MCF-7 cancer lines, given that their killing percentage was found to be 100% at concentration of 1 \(\upmu\)M. The complexes displayed an antiproliferative effect similar to that of doxorubicin at 1 \(\upmu\)M dosage on HEK-293 cell lines and their cytotoxicity decreased with a decrease in the concentration. All the Pd(II) complexes caused a very noticeable modification in the morphology of MCF-7 cancer cells; indeed, the membrane blebbing induced by the apoptotic cell-death was present in cells treated with the complexes and the percentage of the blebbing cells reached to the maximum for all the complexes. [PERSON] et al. (2021) [58] studied a Schiff base ferrocene-palladium(II) complex (**34**) and studied its antiproliferative activity on human liver cancer cells (Sk-Hep-1 e MHCC97-L), human breast cancer cells (MDA-MB-231), human non-small cell lung cancer cells (A549), human non-small cell lung cancer cells resistant to paclitaxel (A549/TAXOL), and mouse embryonic fibroblasts (NIH3T3). It suppressed the viability of different tumor cell lines excellently with a potency up to 20-fold better than cisplatin as well as possessing lower toxicity in normal cells. The highest activity was observed against Sk-Hep-1 (IC\({}_{50}\) = 0.88 \(\upmu\)M versus 18.1 \(\upmu\)M of cisplatin), MHCC97-L (IC\({}_{50}\) = 8.28 \(\upmu\)M versus 38.7 \(\upmu\)M of cisplatin) and NIH3T3 (IC\({}_{50}\) = 8.35 \(\upmu\)M versus \(>\) 100 \(\upmu\)M of cisplatin). The mechanism underlying the antiproliferative activities was suggested to proceed through the induction of the caspase 3-dependent apoptosis in vitro. Additionally, the cellular target of compound **34** was predicted by molecular docking studies, suggesting that it possesses a high affinity to specifically bind the BIR3 domain of XIAP. [PERSON] et al. (2021) [59] studied Pt- and Ru-based complexes, which are two of the most successful chemotherapeutic agents having a significant role in cancer chemotherapy despite their side effects.