title: Three-dimensional quantitative structure activity relationships of quorum-sensing and biofilm inhibitors in gram-negative bacteria.
abstract: 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.
authors.affiliation: Department of Chemistry, Texas Southern University, Houston, Texas 77004, USA.
authors.forename: Brooke
authors.initials: B
authors.lastname: Woodard
authors.forename: Mahmoud A
authors.initials: MA
authors.lastname: Saleh
mesh_terms: 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
chemical_list: D054742:Acyl-Butyrolactones; D000900:Anti-Bacterial Agents