QSAR Analysis of Antimicrobial Activity of 4‐thiazolidone Derivatives

Abstract

AbstractThe influence of molecular structure of 4‐thiazolidone derivatives (about 70 compounds) on their antimicrobial activity has been investigated by QSAR approach based on Simplex Representation of Molecular Structure (SiRMS). This method is characterized by the absence of molecular alignment problem as well as by taking into account the different atom characteristics (partial charge, lipophilicity, etc) and the possibility of drug design. The following micro‐organisms were used as reference cultures: Candida albicans S, Citrobacter freundii, Klebsiella pneumoniae, Pseudomonas aeruginosa (R and S strains) and Staphylococcus aureus MSSA. Statistical characteristics of QSAR models obtained by Partial Least Squares (PLS) method are rather good (R2=0.843–0.989, Q2=0.679–0.864, R2test=0.744–0.943). Y‐scrambling test shows the possibility of chance correlations for equations developed for C. freundii and K. pneumonia. These two cultures were excluded from subsequent analysis. The molecular fragments promoting/interfering with antimicrobial activity and degree of their influence on the activities have been determined. Thus, naphthalene‐substituted fragment (irrespective to its location within the molecule) decreases the antimicrobial activities significantly. The requirements to molecular design were formulated; e.g. highly active compounds must contain indole fragment. In addition, the influence of heterocyclic system evolution on antimicrobial properties of 4‐thiazolidones derivatives was demonstrated. The important role of electrostatic characteristics of their molecular structure was also shown. The compounds with the highest predicted values of antimicrobial activities against several cultures were chosen as a result of virtual screening.