Cancer is considered the second biggest reason for demise after cardiovascular illnesses in most developed countries. It is one of the key targets in treatment. Metal-based compounds were launched in 1978 when Cisplatin was licensed via the US Food and Drug Administration to treat ovarian and testicular malignancies and are a very important family of anticancer medications [1].

Cancer treatment is challenging because of the cancer cells' resistance to many presently utilized treatments. To overwhelm Cisplatin and other drugs' cancer resistance and acute dose-limiting adverse effects, numerous platinum complexes have been created and assessed for their potential to fight cancer. Platinum complexes' promising outcomes are the motives why these categories of composites are still far more studied. On the other hand, no new platinum compounds have moved into clinical studies ago 1999 [2]. Subsequently, a quest for new complexes of non-platinum metal has been improved. Studies are concentrated on drugs with greater efficacy, such as drugs interacting differently with the target (DNA). So, via DNA binding and/or cleaving, many anticancer drugs that can block DNA replication by way of metal complexes have been upgraded [3], [4], [5].

Because platinum(II) and palladium(II) species have structural and thermodynamic similarities, palladium(II) complexes have been investigated as a substitute for compounds containing platinum. It was previously discovered that a considerable percentage of Pd(II) complexes had superior bioactivities in comparison to respective compounds of Pt(II) [6], [7]. Research has also demonstrated that several complexes of Pd(II) show similar [8], [9], [10], [11], [12] or even superior activity than Pt(II)-confirmed medicines [13], [14], [15]. Palladium(II) complexes have diminished Cisplatin cross-resistance, reduced toxicity, and high specificity [16]. Studies utilizing palladium(II) complexes have demonstrated anticancer impacts on cancerous cells. In a study, Pd(II) complexes of N-(5-nitro-salicylidene)-Schiff bases (1–3, [Pd(L)(H2O)].xH2O) were created by Özdemir et al. [17] and investigated the in vitro cytotoxicity against the malignant cell lines HeLa and MCF-7. In contrast to the typical anticancer medication, doxorubicin, complexes 1 and 2 had only moderate antitumor activity against HeLa cell lines. Complex 3 was the most active. Given that all three complexes had a 100% kill rate at a concentration of 1 µM, they were all more potent than doxorubicin against MCF-7 cancer cells. In addition, Sarto et al. [18] describe three recently created Schiff base Pd(II) complexes derived from 4- aminoacetophenone and their in vitro anticancer potential. This study concluded that the newly created complexes exhibit considerable cytotoxic activity against the MDA-MB-435 cell line, particularly complex2 and complex3, which could lower cell viability by more than 80 % after 48 h of treatment.

Nowadays, other metals and their complexes entered the stage as potential drugs having chemotherapeutic, antimicrobial, and antifungal activities [19]. Zinc(II) is one of these metals, considered the second most prevalent metal ion in biological systems and more bio-compatible than platinum. Because of its maximum Lewis acidity, innocent redox characteristics, easy exchange of ligands, adaptable coordination surroundings, and substantial physiological profusion, the zinc(II) ion is the most evident option of nature [20]. To explore the anticancer activity of two Schiff base ligands (L1, L2) and their complexes with Fe(III) and Zn(II), Naureen et al. [21] used a potato disc tumor induction test with strains of the bacteria Agrobacterium tumefaciens. Compared to the comparable Fe compounds, the complexes of the two Schiff bases with Zn in this assay had a greater activity with lesser IC50. The acquired data demonstrated that Zn complexes were more cytotoxic than their Fe counterparts (IC50 > 134 µg/ml). Moreover, Dasgupta et al. [20] prepared three Zn(II) complexes [Zn(L1)Cl2], [Zn(L2)Cl2] and [Zn(L3)Cl2] from 3 acyl hydrazone Schiff base ligands to investigate their anticancer activity using HCT116, HepG2 and A549 cells. [Zn(L2)Cl2] was discovered to be the most effective therapeutic agent for all three cell lines among the three complexes with the lowest IC50, 38.66, 19.83, 41.85 µg/ml for HCT116, HepG2, and A549 cells, respectively. [Zn(L3)Cl2] exhibited the least activity with the highest IC50, 70.44, 66.24, 87.63 µg/ml toward all three cell lines. The three zinc(II) complexes display excellent potential therapeutic characteristics.

It is recognized that the metal center and surroundings around the metal center, quantity of coordinated ligands, coordination geometry, and the locations of the electron donor or acceptor groups in the aromatic ring all impact the biological activities of these compounds. To stabilize the metal complexes and avoid probable cis-trans isomerization, chelating ligands were used to synthesize complexes, and their positive effects have been observed [22], [23], [24]. Some chelators used were of Schiff base types [25], [26], [27], [28]. Schiff bases are considered an influential group of compounds in the pharmaceutical and medical fields [29], [30]. They are a set of ligands and participate in developing coordination chemistry because they facilely create steady complexes with nearly all transition metals [31], [32], [33], [34].

Preparing novel ligands is a substantial step in developing metal complexes to perform certain biological functions. Altering the metal center and ligand surroundings in complexes are two methods for increasing medication selectivity [35], [36], [37]. Moreover, an alteration in the surroundings of metal significantly binds the metal complex to DNA or protein. Various metal ions configurations can influence these derivatives' bioactivity [38], [39].

In this paper, we report for the first time the synthesis and characterization of the Pd(II) and Zn(II) complexes of novel Schiff base made by 2-hydroxybenzohydrazide and (E)− 1-(2-(p-tolyl)hydrazono)propan-2-one. Both complexes and Schiff base ligand were evaluated by MTT assay to find their cytotoxicity towards MCF-7 cells, and IC50 values were determined and compared with Cisplatin as a standard anticancer agent. The results of this present work observed that Out of the synthesized compounds, Zn(II) complex demonstrated superior anti-cancer efficacy. The samples were subjected to oxidative stress, where the activity of GPx, Catalase, and SOD and the level of MDA were examined to assess mechanistic pathways. A comet assay was also conducted to confirm the biological results.