Computer prediction of acute toxicity of thioderivatives of 3,5-bis(5-mercapto-4-R-4H-1,2,4-triazol-3-yl)phenol

This study presents the computational prediction of acute toxicity for new derivatives of 3,5-bis(5-mercapto-4-R-4H-1,2,4-triazol-3-yl)phenols and their alkylated analogues. The aim of the work was to evaluate the impact of structural changes, particularly alkylation and chain length extension, on the toxicity levels of new derivatives of 3,5-bis(5-mercapto-4-R-4H-1,2,4-triazol-3-yl)phenols and their alkylated analogues. Materials and methods. QSAR methodologies were used to predict toxicity, allowing the evaluation of toxicological properties based on molecular descriptors. Toxicity modeling was performed using computer software, enabling the estimation of toxicity without the need for in vivo experimental studies. Results. The results showed, that alkylation of 3,5-bis(5-mercapto-4-R-4H-1,2,4-triazol-3-yl)phenol derivatives does not lead to a significant toxicity reduction. Moreover, an increase in toxicity was observed with the prolongation of the carbon chain in the synthesized compounds. It was also found, that acid derivatives, particularly 2,2’-(((5-hydroxy-1,3-phenylene)bis(4-R-4H-1,2,4-triazol-5,3-diyl))bis(sulfanyl))diacetate acids and 3,3’-((((5-hydroxy-1,3-phenylene)bis(4-R-4H-1,2,4-triazol-5,3-diyl))bis(sulfanyl))bis(methylene))dibenzoyl acids, exhibit toxicity ranging from 521.9 mg/kg to 2232.2 mg/kg, corresponding to toxicity class IV (low toxicity) on the OECD scale. It was found, that molecular structure and hydrophobic properties play a crucial role in determining compound toxicity. This study helps to establish a structure-toxicity relationship and to optimize compound structures for reduced toxicity. Conclusions. These results provide a foundation for further development of potential drug candidates with predicted toxicological properties.