## 3 Results
### New Synthesized Molecules  
Since there is not yet a definite solution for the treatment of cancer, there is a clear need to research new molecules with anticancer properties. The combination of in vitro techniques and molecular docking can also be used also to test new synthesized molecules. Table 3 shows the works in the last five years that have implemented in silico and in vitro models for drug discovery using new synthesized molecules as drugs for metastatic BC. For example, [PERSON] et al. [PERSON] et al. (2018) synthesized a new series of compounds; i.e., new benzimidazole derivatives against BC-targeting peptidylprolyl cis-trans isomerase NIMA-interacting 1 (PIN1). PIN1 proteins play a role in cell cycle regulation, and their overexpression is correlated with human cancer [PERSON] et al. (2018). It has also been described that PIN1 increases DNA binding to estrogen receptors ([PERSON] et al., 2018). Anticancer effects have been tested in vitro with MTT assays using the MCF-7 cell line: Several synthesized compounds have shown a very strong efficacy against this BC cell line. Furthermore, the interactions of three synthesized compounds with PIN1 crystal structures (PDB: 4 TYO) have been validated using molecular docking, and the formed complexes show some essential interactions for PIN1 inhibition [PERSON] et al. (2018). Specifically, the interaction with Lys63 is crucial for PIN1 inhibition. In another study, [PERSON] et al. [PERSON] et al. (2018) synthesized the new hybrid dihydroquinoline derivative (M-CNP) compound. They designed this hybrid compound composed of sulfonamide, quinoline, and chalcone. The idea behind the study was that molecules containing sulfonamide, quinoline, and chalcone could originate new hybrid architectures with novel anticancer properties. The aim is that compounds derived from more molecules can enhance the pharmacological effectiveness. Anticancer activity of the novel compound was demonstrated by regulating aldehyde dehydrogenase 1 family member A1 (ALDH1A1), which, by converting retinal (retinaldehyde) to retinoic acid (RA), plays a role in the differentiation of cells and signaling events. Interestingly, an in vivo test on a metastatic BC cell lines (i.e., MDA-MB-231) has confirmed the promising role of ALDH1A1. Indeed, cytotoxicity assays have demonstrated the specific activity of the compounds against tumor cells. Furthermore, molecular docking analyses have demonstrated that the M-CNP derivative plays a role as an anticancer drug because of its good affinity with ALDH1A1 ([PERSON] et al., 2018). Previous studies have shown that compounds can bind to DNA with covalent and non-covalent interactions; for example, cisplatin, a well-known anticancer drug, interacts with DNA via a covalent link. However, covalent interactions can induce serious side effects, highlighting the importance of non-covalent interactions between DNA and drugs ([PERSON] et al., 2018). Among metal complexes, nickel aroyhydrazone Schiff base complexes show non-covalent interactions. Following this assumption, [PERSON] et al. [PERSON] et al. (2018) synthesized two nickel-derived complexes, and molecular docking revealed that both compounds could bind to DNA through the interaction of the phenyl rings with the double helix. In addition, the association between DNA and bovine serum albumin (BSA) is able to modify the secondary structure of BSA. The anticancer activity of individual complexes was also evaluated with in vitro cytotoxicity assays on the A549, MCF-7, and L-02 cell lines ([PERSON] et al., 2018). Both complexes obtained a lower cytotoxic effect than cisplatin against normal cell lines. Thus, in vitro analysis suggests more selective effects of the compounds against cancer cell lines. Ruarene complexes have been observed to be possible agents against cisplatin resistance with fewer side effects, demonstrating a different mechanism of action. [PERSON] et al.