Evaluation of antimicrobial activity and retention behavior of newly synthesized vanilidene derivatives of Meldrum's acids using QSRR approach.

Increased antimicrobial resistance together with the lack of new antimicrobial drugs suggest on an urgent need for new therapeutics in this field. Vanilidene derivatives of Meldrum's acid present one of the possible approaches. In this work lipophilicity of 13 vanilidene derivatives of Meldrum's acid as well as their predicted antimicrobial activity towards several characteristic species has been evaluated. 10 vanilidene derivatives have been previously synthesized and 3 new compounds are synthetized afterwards following the same procedure. These selected 13 candidates were examined using thin layer chromatography in two different solvent systems. Gained retention parameters were a starting point for further Quantitative Structure Property Relationships (QSRR) studies in which minimum inhibitory concentration (MIC) for Candida albicans, Trichoderma viride, Penicillium italicum, Fuscarium oxysporum, Pseudomonas aeruginosa and Escherichia coli were determined. Statistically significant QSRR models were established and clustering of the compounds was performed with the help of principal component analysis (PCA) and hierarchical cluster analysis (HCA). Absorption, Distribution, Metabolism, and Excretion (ADME) properties of investigated molecules were subjected to sum of ranking differences (SRD) analysis in order to explore their pharmacokinetic properties. SRD analysis was also performed for the ranking of the established QSRR models. It was shown that compounds 6, 8 and 9 possess a significant antimicrobial activity, satisfied ADME properties and these candidates should be further optimized in order to utilize unexplored potential of Meldrum's acid in synthesis of novel antifungal compounds.