title: Design of novel 4-hydroxy-chromene-2-one derivatives as antimicrobial agents.
abstract: This paper presents the design of novel 4-hydroxy-chromene-2 one derivatives, based on previously obtained minimal inhibitory concentration values (MICs), against twenty four microorganism cultures, gram positive and negative bacteria and fungi. Two of our compounds, 3b (MIC range 130-500 microg/mL) and 9c (31.25-62.5 microg/mL), presented high potential antimicrobial activity. The compound 9c had equal activity to the standard ketoconazole (31.25 microg/mL) against M. mucedo. Enlarged resistance of S. aureus, E. coli and C. albicans on the effect of potential drugs and known toxicity of coumarin antibiotics, motivated us to establish SAR and QSAR models of activity against these cultures and correlate biological activity, molecular descriptors and partial charges of functional groups to explain activity and use for the design of new compounds. The QSAR study presents essential relation of antimicrobial activity and dominant substituents, 4-hydroxy, 3-acetyl and thiazole functional groups, also confirmed through molecular docking. The result was ten new designed compounds with much improved predicted inhibition constants and average biological activity.
authors.affiliation: Department of Chemistry, Faculty of Science, University of Kragujevac, P.O. Box 60, Serbia. mmladenovic@kg.ac.rs
authors.forename: Milan
authors.initials: M
authors.lastname: Mladenović
authors.forename: Nenad
authors.initials: N
authors.lastname: Vuković
authors.forename: Slobodan
authors.initials: S
authors.lastname: Sukdolak
authors.forename: Slavica
authors.initials: S
authors.lastname: Solujić
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009089:Mucor / Q000187:drug effects; D021281:Quantitative Structure-Activity Relationship; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000890:Anti-Infective Agents; D003374:Coumarins; C030123:coumarin