## 6 Case Studies of QSAR Modeling of Anti-Breast Cancer Agents
\begin{table}
\begin{tabular}{c c c c c} \hline
**Compound’ Scaffold** & **Cell Line** & **Modeling** & **Software** & **Ref.** \\ \hline Heterogeneity group & MDA-MB-231 & 2D-QSAR & QSARINS v2.2.4 & [271] \\ \hline (_E_)-S-(-2-Arylvinyl)-1,3-4-c=adiazo0-2 & HCT-116,MCF-7 and HeLa & 2D-QSAR & Statistica v13, TIBCO & [272] \\ y!benzenesulffoamides & & & & \\ \hline
2-[(4-Amino-6-N-substituted-1,3,5-triazin-2- \\ y!methylthio!-4)-chloro-5-methyl-N-(1H- \\ benzoe)[2][d][d][radio2-3][\(2H\)] & HCT-116,MCF-7 and HeLa & 2D-QSAR & MOE 2016 & [273]\({}^{\star}\) \\ylidene)[benzeensinfoamides & & & & \\ \hline Arylsulfonylhydrazenes & MCF-7 and MDA-MB-231 & 2D-QSAR & MDL QSAR v2.2 & [274]\({}^{\star}\) \\ \hline
6-bromo-coumarin-ethylene-hydrazanyl- & & & & \\ \hline thiazol and & MCF-7, A-549,and CHO-K1 & 2D- and 3D-QSAR & MOE 2016.08 & [275] \\
6-bromo-coumarin-thiazolyl-based derivatives & & & & \\ \hline
2,6,9-Titsubstituted Purine derivatives & & & & \\ \hline CFADE-1, NCI-H460, HI-60, CACO2, & & & & \\ \hline HCI-16, K52, MCF-7, MRC-5 & 3D-QSAR & Sybj1X-1.2 & [276] \\ \hline Salicylicaldehyde hydrazenes & & & & \\ \hline
2-phenylacrylonitrile & MCF-7 & 2D-QSAR & winMolconn v. 1.0.2.1 & [278] \\ \hline Novel series of 2-(4-fluorophenyl) & & & & \\ \hline imidazol5-ones & & & & \\ \hline Pyrazole derivatives & PC-3, Bi6710, K526, MDA-MB-231, & & & \\ \hline DJhydropyrimidine derivatives & MCF-7 & 2D-QSAR & QSARINS & [281] \\ \hline N-substituted benzimidazole derivatives & HCT 116, H 460, MCF-7 and HEK 293 & 3D-QSAR & VolSurf+ 3-D & [282] \\ \hline
2-[(4-Amino-6-N-substituted-1,3,5-triazin-2- \\ y!methylthio!-N-(imidazol-2 ylidene)+)-chloro-5-methyl-benzenesulffoamides & HCT-116,MCF-7, HeLa, HaCAT lines & 2D-QSAR & STATISTICA software v.13 & [283]\({}^{\star}\) \\ derivatives & & & & \\ \hline Hydroxyquinoline scaffold derivatives & MDA-MB-435 & 2D-QSAR & na & [284] \\ \hline \end{tabular} \({}^{\star}\) QSAR models were subsequently employed for the design, synthesis, and experimental testing of novel compounds; na—not available.  
\end{table} 
Table 6: QSAR studies based on activity data from various cell lines. ROCK1 and ROCK2 inhibitors [267]. The researchers developed two 3D-QSAR models for these systems, utilizing 34 and 32 compounds from the literature for the training sets and 15 compounds for each test set. Initially, the compounds were divided into four structural clusters, carefully modeled, and optimized at varying computational levels (semi-empirical and ab initio calculations). These compounds were subsequently docked into their respective binding sites, and the resulting bioactive conformations were used for alignment and the calculation of GRIND 3D descriptors. To identify the most significant GRIND variables, a fractional factorial design was applied, and these variables were then incorporated into PLS regression. The authors conducted an in-depth discussion of the 3D-QSAR models, identifying key structural features such as moieties, substituents, linkers, and optimal distances, as well as their favorable and unfavorable contributions to biological activity. Common structural characteristics for both ROCK1 and ROCK2 were also summarized. Additionally, the intermolecular interactions derived from Molecular Docking calculations were thoroughly examined for both systems. The insights gained from the 3D-QSAR models and Molecular Docking studies were employed to design and synthesize nine novel ROCK inhibitors. These compounds were docked into both binding sites, and their predicted intermolecular interactions were analyzed in detail. Experimental testing of the compounds against ROCK1 and ROCK2 revealed that compound **C-19** stood out, displaying remarkable activity, with experimental pIC\({}_{50}\) values deviating by only 0.4 units from the predicted values. Further testing showed that **C-19** strongly inhibited ROCK1 (72.64%) and demonstrated potent anticancer effects, including enhanced apoptosis and cell cycle modulation, particularly in pancreatic cancer cell lines.