Three-dimensional quantitative structure activity relationships of quorum-sensing and biofilm inhibitors in gram-negative bacteria.
Thirty N-acyl homoserine lactone (AHL) analogs with variable antibacterial activity and displaying inhibition of biofilm formation were selected to develop models for establishing three-dimensional quantitative structure-activity relationships (3D-QSAR). Comparative molecular field analysis (CoMFA) and comparative similarity indices analysis (CoMSIA) were carried out to determine the optimum structural requirements for selectivity and potency of quorum-sensing and bacterial biofilm inhibition. The best CoMFA model predicted a q2 value of 0.519 and an r2 value of 0.984 and revealed that electrostatic and steric properties play a significant role in potency and selectivity. The CoMSIA model predicted a q2 value of 0.411 and an r2 value of 0.938 based on a combination of steric, electrostatic, and hydrophobic effects. The analysis of the contour maps from each model provide insight into the structural requirements for increasing the activity of a compound. Consequently, manipulating the chemical and physical properties of substituted acyl groups on the homoserine lactone moiety can provide important information toward enhancing the antibacterial properties of the target chemical compound.
Woodard
Brooke
B
Department of Chemistry, Texas Southern University, Houston, Texas 77004, USA.
Saleh
Mahmoud A
MA
D054742:Acyl-Butyrolactones / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000502:physiology*; D008956:Models, Chemical; D011237:Predictive Value of Tests; D021281:Quantitative Structure-Activity Relationship; D053038:Quorum Sensing; D055672:Static Electricity
D054742:Acyl-Butyrolactones; D000900:Anti-Bacterial Agents