Antimicrobial activity and cytotoxicity of some 2-amino-5-alkylidene-thiazol-4-ones.
We report a small, focused library of 30 diverse 2-amino-5-alkylidene-thiazol-4-ones that was assayed in a whole-cell antibacterial screen against a panel of several bacterial strains and a yeast. Most of the compounds exhibited modest to significant antibacterial activity against Pseudomonas aeruginosa, Bacillus subtilis and Staphylococcus aureus, and no activity against Salmonella typhimurium and Escherichia coli. The antibacterial activity depends markedly upon substituents on the thiazol-4-one core, and the most potent compound assayed ([Formula: see text]-4-((2-(4-methylpiperidin-1-yl)-4-oxothiazol-5(4H)-ylidene)methyl)benzonitrile) reached a minimal inhibitory concentration (MIC) value of [Formula: see text] on P. aeruginosa strain. An important feature of the tested compounds is their low influence on cell viability, as determined in a HEK-293 metabolic activity assay. In light of the encouraging in vitro antimicrobial assay results against several bacterial strains, we have generated a pharmacophore model using the Discovery studio 3.0 package (Accelrys Inc., San Diego, USA), which exposed the spatial arrangement of key molecular properties responsible for our observed MIC results. Considering the absence of a defined target and the limitation of the described approach to pool different scaffolds, the calculated pharmacophore model could be used for library enrichment to identify compounds with a thiazolidinone scaffold with improved antimicrobial potency and physico-chemical properties.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 , Ljubljana, Slovenia.
Marko
M
Jukič
Aleksandra
A
Đorđević
Jelena
J
Lazarević
Martina
M
Gobec
Andrija
A
Šmelcerović
Marko
M
Anderluh
D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D057809:HEK293 Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity
D000890:Anti-Infective Agents; D013844:Thiazoles