## 3 Results
### New Synthesized Molecules
synthesized four ruarene complexes and characterized them using X-ray crystallography ([PERSON] et al., 2018), and molecular docking was performed to demonstrate their ability to bind tubulin proteins (PDB: 1 SA0). The cytotoxicity of the molecules was tested in vitro by MTT assays in three different cancer cell lines, including MDA-MB-231. The complexes that demonstrated a lower toxicity were selected to test their effect on the inhibition of the microtubule network in the MDA-MB-231 cell line. In silico and in vitro studies demonstrated good binding between the compounds and the tubulin, as well as antiproliferative action against advanced subtypes of cancer, such as triple-negative metastatic BC ([PERSON] et al., 2018). _Glycyrrhiza glabra_, an Indian therapeutic herb, contains a diglucopyranosiduronic acid of glycyrrhetic acid (GA). GA plays a role in immune responses, cell cycle, apoptosis, and autophagy ([PERSON] et al., 2018). [PERSON] et al. [52] designed five glycyrrhetic acid (GA) derivatives and analyzed their in vitro action in a metastatic breast cancer cell line (i.e., MDA-MB-231). Molecular docking studies have been carried out to investigate the action of compounds on BC targets such as glyoxalase-I (GLO-I). BC receives energy from glycolysis based on the Warburg effect, and GLO-I is able to inhibit and inactivate methyl glyoxalases, a compound formed during glycolysis, making GLO-I inhibitors potential anticancer agents. It has been shown that GA-1 increases cytotoxic action, and a study using molecular docking confirmed the binding of GA derivatives with GLO-I [52]. As previous studies have described that epidermal growth factor receptor tyrosine kinase (EGFR-TK) is upregulated in BC, it has been suggested as a potential drug target for novel therapy agents. The EGFR-TK inhibitory activity of known 1,3,5-triazines derivatives against BC has been examined [53]. In addition, the effects of the compounds on several BC cell lines have been estimated, including MDA-MB-231, a metastatic BC cell line. The consequence of the compounds on \(\beta\)-catenin expression has also been evaluated: all designed compounds achieved a good binding energy against the target protein. Furthermore, in vitro experiments have confirmed the docking analysis since the synthesized derivatives demonstrated an inhibitory effect on EGFR-TK [53]. Rac family small GTPase 1 (RAC1) is involved in the migration and invasion of BC cells. Therefore, therapeutic strategies that silence RAC1 could be a new challenge [54]. A new series of carbazole derivatives have been designed for their antitumor properties. [PERSON] et al. evaluated the role of the compounds via interactions with RAC1 through molecular docking: the molecular docking results indicated a favorable conformation of the receptor-ligand complex. The compounds also demonstrated moderate antiproliferative activity using in vitro techniques [54]. The main site of BC metastasis is bone, and bone metastases often lead to complications, including fractures, bone pain, and hypercalcemia. However, to date, no biomarkers have been identified that are able to predict bone metastases. A first circulating fragment of parathyroid hormone-related protein (PTHrP), PTHrP(12-48), has been proposed as a biomarker associated with the presence of bone metastases. [PERSON] et al. [55] investigated the biological processes and mechanisms of action of PTHrP(12-48). First of all, they predicted the tertiary structure of PTHrP(12-48) through bioinformatics analyses, and the molecular modeling found that PTHrP(12-48) interacts via a weak binding with the PTH1 receptor (PTHR1). In vitro analysis supported this model: PTHrP(12-48) treatment does not promote an increase in cAMP in PTHrR1-expressing SaOS2 cells. In conclusion, these data indicate that PTHrP(12-48) acts in the regulation of the differentiation of hematopoietic cells and regulates the osteoclasts within the tumor-bone marrow microenvironment, possibly to induce bone metastasis [55].