title: Relationship between drug structure and minimal inhibitory concentration value used for acceptable daily intake analysis.
abstract: The minimal inhibitory concentration (MIC) of an antimicrobial agent for a microbial population (MIC(50, obs) and MIC(90, obs)) is an interpolated value determined for antibacterial drugs by in vitro methods. Many studies have tried to determine the correlation between the MIC(50, obs) or MIC(90, obs) value and the physicochemical parameters to allow quantitaive structure activity relationship (QSAR) predictions of efficacy. A rigorous evaluation of approaches to this problem is presented here. In order to find a correlation between chemical structure and the derivatives of the MIC values for 9 indicatory bacterial strains, it is necessary to employ a number of physicochemical parameters in combination. Only an arithmetic expression composed of many features illustrating the chemical structure of the molecule can be linked to the ƒMIC(50, obs) value. This article demonstrated that, despite the complexity of the MIC value used as the end point, it is possible to validate the model in a limited extent.
authors.affiliation: Polpharma Biologics, Trzy lipy, Gdańsk, Poland tomasz.grabowski@polpharma.com.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Grabowski
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego, Olsztyn, Poland.
authors.forename: Jerzy Jan
authors.initials: JJ
authors.lastname: Jaroszewski
authors.affiliation: Gad Consulting Services, NC, USA.
authors.forename: Shayne Cox
authors.initials: SC
authors.lastname: Gad
authors.affiliation: Department of Research and Development, ADAMED Sp. z o.o., Pieńków, Czosnów, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Feder
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D008962:Models, Theoretical; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents
keywords: ADI; MIC; MRL; in silico; structure; validation