## 3 Results
### New Synthesized Molecules
Angiogenesis, a physiological process that produces new blood vessels from pre-existing blood cells, consists of a series of steps such as the production of protease, endothelial cell migration and proliferation, vascular tube formation, and the maturation of cells [56]. Accelerated angiogenesis is correlated with several diseases, including cancer. The inhibitors of angiogenesis that target several proteins, such as vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and basic fibroblast growth factor (bFGF), that are involved in the regulation of the process can be used as a therapeutic strategy. The main factor in the angiogenesis process is VEGF [56]. [PERSON] et al. [57] designed 7-chloro-4-(piperazin-1-yl)quinoline derivatives as VEGFR-II inhibitors, and the anticancer abilities of these compounds were tested in vitro using breast cancer and prostate cancer cell lines. These analyses demonstrated that compound \(\mathbf{4q}\) is the most active on both cell lines, and molecular modeling revealed that \(\mathbf{4q}\) has similar sites of binding as sorafenibib and lenavatinib at the ATP binding site of VEGFR-II. Furthermore, the binding energy of \(\mathbf{4q}\) is slightly better than that of lenavatinib but lower than that of sorafenibib [57]. Apoptosis is one of the key hallmarks of cancer. The BCL-2 family is a group of proteins that have a fundamental role in the regulation of apoptosis. For this reason, BCL-2 has become one of the most studied drug targets over recent years. [PERSON] et al. [58] designed a 3D pharmacophore model to act as an inhibitor of the antiapoptotic BCL-2 protein. The 15 oxadiazole derivative compounds were tested to demonstrate their inhibitory activity in two cancer cell lines (i.e., cervical HeLa and breast MDA-MB-231). Molecular docking was carried out to evaluate the interaction scores between the compounds and the BCL-2 protein. Some of the proposed compounds obtained good antiproliferative activity and good binding energy with the BCL-2 protein (compounds **1** and **16j**) [58]. The simplicity of the synthesis of these compounds and their low molecular weight is promising; therefore, additional studies should be employed based on this novel class of BCL-2 inhibitors. Oncogenic proteins such as tyrosine kinases, cell cycle regulators, and transcriptional factors are implicated in metastatic pathways in cancer. Many of them interact with heat shock protein 90 (Hsp90). Therefore, Hsp90 inhibitors have been proposed as novel cancer treatment methods, although they can lead to adverse effects in clinical trials. To overcome these disadvantages, [PERSON] et al. [59] designed novel molecular Hsp90 inhibitors. Specifically, they designed novel pyrimidine acyl thiourea derivatives as Hsp90 inhibitors, and in vitro analyses revealed that these compounds can inhibit cell proliferation and demonstrate cytotoxic effects in BC and human bone osteosarcoma cell lines. Molecular docking confirmed the interaction of these compounds with the Hsp90 domain [59]. Previous studies have suggested KDM5A and KDM5B as oncogenic regulators [60]. The catalytic domain of KDM5 proteins has an unusual inclusion of an ARID and PHD1 domain that divides the catalytic domain into two subdomains--namely, JmjN and JmjC. [PERSON] et al. demonstrated that a deletion of the ARID and PHD1 domains has a negative impact on the in vitro enzymatic kinetics of the KDM5 family. Thus, the challenge is finding inhibitors that act on the catalytic domain of the KDM5 family; to this end, the authors proposed GSK-J1 as an inhibitor of the KDM family through in silico studies [61]. EPH receptor A2 (EphA2) is a receptor tyrosine kinase that is involved in drug resistance and metastatic processes [62]. [PERSON] et al. designed agonistic peptides that target the ligand-binding domain of the EphA2 receptor, called 135H11 and 135H12 [63].