## 4 Discussion  
In our experiments, Les-4368 in the 10-100 \(\upmu\)M concentration range induced a decrease in resazurin reduction in both studied (CACO-2 and BJ) cell lines in a similar way. Similarly, Les-4370 also decreased resazurin reduction in both studied cell lines but only when applied at the highest \(\upmu\)M concentration. The toxicity of Les-4368 was confirmed by the increase in LDH release in both studied cell lines exposed to the 10-100 \(\upmu\)M concentrations of the compound (Figure 13). Interestingly, an increase in LDH after the treatment of CACO-2 cells with Les-4370 was observed only at the concentration of 50 \(\upmu\)M, while an increase in LDH release in the BJ cell line was observed in the 50 nM and 100 \(\upmu\)M concentration variants. Les-4370 decreased the resazurin reduction less than Les-4368, which may suggest that despite the toxicity of Les-4370, metabolism and/or cell number were not significantly reduced. This was confirmed by calculating LD\({}_{50}\) and IC\({}_{50}\) for both compounds and tested cell lines. Therefore, we conclude that the Les-4368 compound is more toxic in both cell lines than Les-4370. The experiments conducted by [PERSON] et al. demonstrated an increase in LDH release in BJ cells after exposure to ethyl _rel_-[(5a_R_,11b_R_)-10-bromo-2-oxo-5a,11b-dihydro-2\(H\),5_H_-chromeno[42-oxo-5a,11b-dihydro-21l][1,3]thiazol-3(6_H_)-yl] acetate (Les-2769) (50-100 \(\upmu\)M) and Les-3266 (10-100 \(\upmu\)M) [10]. However, in the SCC-15 line, Les-3266 and Les-2769 induced LDH release at high micromolar concentrations of 10-100 \(\upmu\)M (Les-3266) and 100 \(\upmu\)M (Les-2769) [10]. To date, an increase in LDH release by 4-TZD derivatives has been observed in healthy BJ cells exposed to Les-236 (10-100 \(\upmu\)M) [12]. In the same research, it was noted that Les-236 was significantly more toxic and caused LDH release in SCC-15 cells at concentrations of 1-100 \(\upmu\)M when compared to normal cells [12]. In studies of SCC-15 cells treated with Les-2194, Les-3640, and 5,10-dihydro  
Figure 12: Molecular docking of Les-4370 with PPAR\(\gamma\). 2H-benzzo[6,7]thiochromeno[2,3-d][1,3]thiazole-2,5,10-trione (Les-3377) at the concentration range from 1 nM to 100 \(\upmu\)M, an increase in LDH release was observed when the cells were exposed to these compounds at the higher concentrations of 10-100 \(\upmu\)M [9]. [PERSON] et al. showed that all tested compounds (2-[2-[3-(benzothiazol-2-ylamino)-4-oxo-2-thioxothiazol-5-ylidenemethyl]-4-chlorophenyloneoxy]-N-(4-methoxyphenylyl)-acetamide) (Les-3166), 7-oxa-10-thia-8-aza-cyclopenta[b]phenanth-9-one (Les-5935), Les-6009, and Les-6166 used at a concentration from 10 to 100 \(\upmu\)M were able to reduce metabolic activity in BJ, SH-SY5Y, and A549 cell lines [11]. Moreover, it has been proved that Les-2769 and Les-3266 also decreased metabolic activity in SCC-15 and BJ cell lines [10]. Similarly, [PERSON] et al. reported that Les-2194, Les-3640, Les-5935, and Les-6166 decreased resazurin reduction in the 3T3-L1 cell line. When the 3T3-L1 cells were exposed to Les-2194, Les-3640, Les-5935, or Les-6166 at the concentrations of 100 nM, 1 \(\upmu\)M, 10 \(\upmu\)M, 50 \(\upmu\)M, and 100 \(\upmu\)M, it was observed that 100 \(\upmu\)M Les-2194 and Les-3640 induced a decrease in resazurin reduction [33]. [PERSON] et al. proved the effectiveness of a 4-thiazolidinore derivative 5-bromo-3-[2-[5-(4-methoxyphenylyl)-3-naphthalene-2-yl-4,5-dihydroxypyrazol-1-yl]-4-oxo-4,5-dihydro-1,3-thiazol-5-ylidene]-2,3-dihydro-1H-indol-2-one(Les-3833) against human melanoma (WM793) cells. In melanoma cells, Les-3833 induced apoptosis through morphological changes and an increase in the amount of pro-apoptotic proteins, ROS production, and arrest of the G0/G1 phase of the cell cycle [41]. It is known that apoptosis is often caused by a high increase in ROS production [42]. To date, ROS-induced caspase-3 activity has been well described [43]. Therefore, in the next part of our study, we decided to study these parameters.