QSAR Studies on Some C-21 Mercapto Derivatives as AntiPulmonary Inflammatory Agents

Abstract

Glucocorticoids have been widely used for the treatment of inflammatory conditions but are associated with various side effects. C-21 mercapto derivatives, a class of dissociated steroids, have shown potential as anti-inflammatory agents with reduced side effects. In this study, QSAR (Quantitative Structure-Activity Relationship) analysis was performed on a series of 19 C-21 mercapto hydrocortisone derivatives with IL-6 cytokine inhibition activities. Molecular descriptors were calculated using Alva descriptor software, and significant descriptors governing the activity were identified. Multiple linear regression analysis revealed statistically significant models, and the best two-variable model included spectral mean absolute deviation from reciprocal squared geometrical matrix (SpMAD_RG) and H autocorrelation of lag 3 weighted by i state (H3s). Internal and external validation confirmed the reliability of the models. The study suggests that these structural descriptors, particularly SpMAD_RG and H3s, play a crucial role in the activity prediction of C-21 mercapto derivatives. The findings contribute to the design of novel molecules in this class with improved therapeutic potential.