## 4 Discussion
With regard to toxicity to the immune system, most compounds showed active toxicity, while only 10 compounds demonstrated inactive toxicity. On the other hand, mutagenic activity was non-existent for most of the compounds, with the exception of piptolinic acid E, which showed active cytotoxicity. Regarding the BBB barrier, most of the compounds showed potential toxicity, but only four showed inactive toxicity. Many compounds were innocuous in terms of ecotoxicity, but 15 may have some effect on the environment. Regarding clinical and nutritional toxicity, most of them pose some danger to human health. The results of the evaluation of toxicity in the nuclear receptor signaling pathways showed that all compounds analyzed did not show toxicity towards receptors such as AhR, ER-LBD, aromatase, and PPAR-Gamma, indicating reduced potential for interference in the endocrine and metabolic systems. With regard to the ER receptor, only ofticimalonic C and ganoderic T acids showed toxic activity. As for the AR and AR-LBD receptors, there was a more marked variation in the results, suggesting variations in the interactions of the compounds with these targets. The results showed that most of the compounds analyzed regarding the stress response pathways exhibited inactive toxicity in the markers evaluated, indicating low potential to cause stress in cells. Notably, no compounds exhibited active toxicity in the p53 and ATAD5 markers, which is significant as it suggests a lack of interference in critical pathways for tumor suppression and the maintenance of DNA integrity, which are essential factors in preventing carcinogenesis. The tumor suppressor p53 is often called the 'guardian of the genome' because of its crucial role in preserving genomic stability [50]. ATAD5 also plays a vital in preserving genomic stability [51]. The toxic inactivity profile indicates a rescued risk of causing or promoting cancer, corroborating the genomic safety of the compounds. In the prediction of toxicity in molecular initiating events, all compounds showed inactive toxicity regarding the THR\(\beta\), RYR, NMDAR, AMPAR, KAR, CAR, VGSC, and NIS receptors. However, regarding the THR\(\alpha\) receptor, the compounds ganoderic acid W, H, X, and F, aurisin A, inoscavin A, lanostanoid 3, and otificimalonic acids F, E, and G showed active toxicity. In the TTR, only aurisin A, inoscavin A, and lanostanoid 3 showed active toxicity. For the GABA receptor, most of the compounds showed inactive toxicity, but 47 of the compounds were active. With regard to AChE, only the compounds tariquidar and colossolactone H showed active toxicity. In NADHOX, the compounds (3\(\beta\),5a,8a,22E)-5,8-epidoxyergosta-6,22-dien-3-yl \(\beta\)-D-glucopyranoside, eringiacetal A, otificimalonic acids C, and colossolactone H showed active toxicity. For the PXR receptor, there was greater variability. In the toxicity assessment in terms of metabolism, all compounds were considered non-toxic to the cytochromes CYP1A2, CYP2C19, CYP2D6, and CYP2E1--enzymes that perform essential functions in the metabolism of medicines and substances [37]. However, 12 compounds showed toxicity to cytochrome CYP2C9. The control tariquidar and compound inonotusol F showed toxicity to cytochrome CYP3A4. Finally, the pharmacokinetic characteristics were evaluated to identify promising modulators of P-gp activity. Based on the analyses of the ADME parameters and the scoring system developed, it was possible to identify that six compounds showed better pharmacokinetic potential than our control. The compounds with the highest scores (ADME = 4) and selected as the most promising from this screening were ergosta-4,6,8(14),22-tetra-3-one, lucidumol A, anticin K, (22E,245)-ergosta-4,22-dien-3-one, 3,11-dioxolanosta-8,24(Z)-diene-26-oic acid, and (22E)-19-norergosta-5,7,9,22-tetra-3\(\beta\)-ol, which obtained the same scores as the control, tariquidar. These compounds stood out for their excellent oral bioavailability, proven by their predicted high absorption in the GI system.