## 3 Results and Discussion
### Molecular Docking
#### 3.3.2 The Caspase-3  
Caspase-3, commonly referred to as ca3, belongs to the family of cysteine-aspartic acid proteases. It is present in the form of procaspases, which are precursor enzymes. Caspase-3 plays a significant role in actively breaking down proteins through proteolysis, particularly in the process of apoptosis [54], Apoptosis is a crucial physiological mechanism responsible for regulated cell death, essential for proper organismal development. Ca3 specifically targets vital structural proteins, cell cycle proteins, and DNase proteins like poly(ADP-ribose) polymerase, gelsolin, and DNA-dependent kinase [55]. Nevertheless, caspases have been found to have roles beyond apoptosis. Research has revealed that ca3, in particular, can facilitate the growth of cancer cells under stress, as well as enhance cellular migration, invasiveness, and tumor angiogenesis [56; 57; 58; 59]. As a result, inhibiting ca3 has been shown to improve the effectiveness of chemotherapy and reduce the occurrence of spontaneous tumor development [60]. Upon activation, following apoptotic signaling events, ca3 focuses on cleaves proteins that possess the Asp-Glu-Val-Asp (DEVD) sequence motif [61]. This process is facilitated by specific residues, namely: Cys163, Gly238, and His121, which stabilize the peptide bond cleavage of the target protein within the active site. The crystal structures of ca3 have revealed its binding affinity to the (1S)-2-oxo-1-phenyl-2-[(1,3,4-trioxo-1,2,3,4-tetrahydroisoquinolin-5-yl)amino]ethyl acetate (RXB) inhibitor. RXB has the ability to irreversibly inhibit it, with its effectiveness dependent on the presence of 1,4-dithiothreitol (DTT) in vitro and dihydropliopic acid in vivo, as well as oxygen through redox cycling. Docking validation has demonstrated that RXB binds to the active site located between  
Figure 1: The 3D structure shows the most favorable FAK complex after docking, with the inhibitor (Mol5) displayed in stick form and colored using default atom colors. chains C and A and primarily engages in hydrophobic interactions with Leu168 and Phe256 from chain A. The isoquinoline moiety of RXB exhibited the highest reactivity. Mol1 exhibits a moderate PLPChem score compared to other compounds that target Ca3, thereby providing a better explanation for its moderate stability when compared to the case of the FAK target. This suggests that Mol1 could serve as a model for Ca3. Notably, Mol1 forms crucial interactions with key residues involved in proteolysis, forming three hydrogen bonds with Thr166 and Leu168, as well as five hydrophobic interactions with Phe256, Tyr204, and Leu168. Additionally, a Pi-sulfur interaction was observed with Cys170. The interactions observed were mainly with residues located in chain A, except for Tyr204, which is from chain C. These interactions confirm Mol1's affinity for Ca3, and all its functions are involved. Mol2 outperformed Mold in terms of their PLPChem scores (Table 5), favoring Mol2 as it secured the third rank among all compounds. Mol2 bound closely to multiple key residues from both chain C and Chain A, giving it a significant advantage over Mol4. The stabilization of Mol2 primarily relied on hydrophobic interactions, as it formed bonds between its amine imidazole and dibromo-pyrrole rings with the two-leucine residues from both chain A and C, along with two other residues from chain C (Thr166 and Phe256). These interactions caused Mol2 to adopt an angle shape of 120\({}^{\circ}\), effectively linking the two chains and blocking the proteolysis site. On the other hand, Mol4 is also bound to Leu168 from chain A and three other residues from chain C (Phe256, His121, and Tyr204). However, the positioning of its 5,6-dibromo pyrrole pyrimidine ring near His121 led to an unfavorable cyclization in the dibromo-pyrrole, potentially impacting its PLPChem score and overall stability. Nonetheless, Mol4 still represents a good model for Ca3, as it interacts with the necessary key residues involved in proteolysis.