Nowadays cancer is one of the leading causes of mortality worldwide and chemotherapy has been shown to be the most successful approach for treating cancer [[1], [2], [3]]. Till now platinum-based drugs are mostly used for the treatment of cancer. However, these drugs have some side effects, like nephrotoxicity, neurotoxicity, and very poor selectivity towards tumour cells [[4], [5], [6], [7]]. The development of drug resistance during treatments is another major drawback of these anticancer drugs [8]. Therefore, in recent years alternative strategies developing novel non‑platinum-based transition metal drugs that are more effective and have lesser side effects have received a lot of interest [9,10].

In this regard, copper-coordinated complexes have drawn special attention for their biological redox potential and strong nucleobase affinity. It is an essential naturally occurring mineral element for most aerobic organisms [11]. Also, in daily life, the human body needs an appropriate amount (1.3–1.6 mg) of this metal to stay healthy [12], and in the body, it is present in both the oxidized (Cu2+) and reduced (Cu+) states. There are already many reports in the literature that recommend that Cu-complexes can be a better alternative to many platinum-based drugs [[13], [14], [15], [16], [17]], as they can interact effectively with DNA through non-covalent interactions and can also prevent uncontrolled cell division. Cu(II) complexes are involved in a wide range of biological processes, including electron transfer, the dioxygen transport system [[18], [19], [20]], the treatment of chronic diseases [21,22], the development of biosensors [23,24], and the production of antimicrobials and antiparasitic drugs [25,26]. In addition to that, there are many important cellular effects like neurotransmission and cellular respiration [27,28] where copper plays a major role. Besides that, the coordination environment around the Cu-center also plays an important role in stimulating pharmaceutical activities. Notably, copper(II) complexes incorporating tetradentate Schiff base ligands have been discovered to have a variety of biological applications including antioxidant [29], anticancer [30], and antibacterial properties [31], as well as applications in nucleic acid chemistry [32]. This has motivated us to develop some new copper-based metallodrug. This overall progress and significance in the area have motivated us to develop new copper-based metallodrugs.

Moreover, in developing and designing a new anticancer metallodrug, the key factor is the correct selection of ligands which also has a vital role in drug design. In this respect, transition metal complexes of tetradentate symmetrical salen ligands have drawn attention of the researchers due to their simple synthesis, stability, chelating properties, interesting structural characteristics, and potential biological applications [[33], [34], [35], [36]]. They mostly exhibit antidiabetic, antiproliferative, antimalarial, antifungal, and antibacterial properties [30,34,35,37]. Also, metallosalens have been employed as anticancer agents because they have similar ligating groups to those found in metalloproteins and enzymes [35,38,39]. They are the well-known DNA-targeting substances and bioinorganic model compounds [40,41]. Apart from symmetrical salen ligands, unsymmetrical tetradentate Schiff base salen ligands are known [26,[42], [43], [44], [45], [46]] for their numerous advantages over their symmetrical counterparts. Mainly when it comes to elucidating the chemical composition and geometry of the metal ion as compared to the symmetrical ones [47]. In addition, unsymmetrical salen ligands are much less studied than symmetrical salen ligands. This is due to the fact that they are much more difficult to synthesize. As a result of the scaffold's asymmetric nature, we can further fine-tune its structure by adding electron-withdrawing and/or electron-donating groups to the edges of both salicylideneamine units [48,49].

Another factor to discuss is the interaction of DNA with metal complexes which has drawn considerable attention. Because metal complexes can bind to DNA under physiological conditions and are being evaluated as potential candidates for use as therapeutic agents [50]. The interaction of metallodrugs with DNA could damage or obstruct the synthesis of DNA in cancer cells, which can cause cell death [51,52]. Moreover, there are many articles that claim copper(II) complexes have stronger DNA binding ability and exhibit better cytotoxicity [[53], [54], [55], [56]]. Most Cu(II) complexes interact strongly with DNA because of their distorted square planar geometry with vacant axial sites, which can facilitate strong DNA interactions [57].

Even though there are a number of salen-Cu(II) complexes [30,35,[58], [59], [60]], Cu(II) coordinated unsymmetrical salen complexes are very few [44,61,62] and their biological applications have not been well explored yet [63,64]. Therefore, keeping these above observations in mind along with our ongoing works on the development of metal-based anticancer agents [14,36,[65], [66], [67], [68], [69], [70], [71], [72], [73], [74], [75], [76], [77], [78], [79], [80], [81], [82], [83], [84], [85], [86], [87], [88], [89], [90], [91], [92], [93]] here we have reported three new unsymmetrical ligands and their corresponding copper(II) complexes (1–3). Physicochemical techniques like elemental analysis, IR, UV–vis, NMR, and HRMS spectrometry were used to successfully characterize all three complexes including SC-XRD analysis to determine the molecular structures of all. The CT-DNA interaction of 1–3 was evaluated using UV − vis and fluorescence spectroscopy along with circular dichroism. Lastly, the cytotoxicity activities of the complexes were studied against two cancers (HeLa and A549) and normal (NIH-3T3) cell lines. The mode of cell death of the three complexes was further evaluated by DAPI, acridine orange/ethidium bromide (AO/EB) and Annexin V-FITC/PI double staining assays. Overall, this study effectively outlined the significance of unsymmetrical salen ligands towards the potential of Cu(II) complexes to their DNA binding and cytotoxicity activities.