Lipophilicity evaluation of some thiazolyl-1,3,4-oxadiazole derivatives with antifungal activity.

The chromatographic behavior of a series of thiazolyl-1,3,4-oxadiazoles with antifungal activity was studied by reverse-phase thin-layer chromatography (RP-TLC). The lipophilicity parameters derived from RP-TLC were correlated with the data derived from liquid-chromatography mass-spectrometry. Good linear relationships were observed between the chromatographic lipophilicity parameters and the theoretical lipophilicity descriptors (logP) generated by various computer software and internet modules. Principal component analysis, applied on the experimental chromatographic lipophilicity indices and the theoretically calculated logP, enabled us to obtain a lipophilicity chart for better vizualization of the similarities and differences of the investigated compounds, which were grouped by k-means clustering in two congeneric classes.

COX Inhibition Profile and Molecular Docking Studies of Some 2-(Trimethoxyphenyl)-Thiazoles.

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used therapeutic agents that exhibit frequent and sometimes severe adverse effects, including gastrointestinal ulcerations and cardiovascular disorders. In an effort to obtain safer NSAIDs, we assessed the direct cyclooxygenase (COX) inhibition activity and we investigated the potential COX binding mode of some previously reported 2-(trimethoxyphenyl)-thiazoles. The in vitro COX inhibition assays were performed against ovine COX-1 and human recombinant COX-2. Molecular docking studies were performed to explain the possible interactions between the inhibitors and both COX isoforms binding pockets. Four of the tested compounds proved to be good inhibitors of both COX isoforms, but only compound A3 showed a good COX-2 selectivity index, similar to meloxicam. The plausible binding mode of compound A3 revealed hydrogen bond interactions with binding site key residues including Arg120, Tyr355, Ser530, Met522 and Trp387, whereas hydrophobic contacts were detected with Leu352, Val349, Leu359, Phe518, Gly526, and Ala527. Computationally predicted pharmacokinetic profile revealed A3 as lead candidate. The present data prove that the investigated compounds inhibit COX and thus confirm the previously reported in vivo anti-inflammatory screening results suggesting that A3 is a suitable candidate for further development as a NSAID.

New 2-Phenylthiazoles as Potential Sortase A Inhibitors: Synthesis, Biological Evaluation and Molecular Docking.

Sortase A inhibition is a well establish strategy for decreasing bacterial virulence by affecting numerous key processes that control biofilm formation, host cell entry, evasion and suppression of the immune response and acquisition of essential nutrients. A meta-analysis of structures known to act as Sortase A inhibitors provided the starting point for identifying a new potential scaffold. Based on this template a series of new potential Sortase A inhibitors, that contain the 2-phenylthiazole moiety, were synthesized. The physicochemical characterisation confirmed the identity of the proposed structures. Antibacterial activity evaluation showed that the new compounds have a reduced activity against bacterial cell viability. However, the compounds prevent biofilm formation at very low concentrations, especially in the case of E. faecalis. Molecular docking studies performed estimate that this is most likely due to the inhibition of Sortase A. The new compounds could be used as add-on therapies together with known antibacterial agents in order to combat multidrug-resistance enterococcal infections.

Synthesis, lipophilicity and antimicrobial activity evaluation of some new thiazolyl-oxadiazolines.

BACKGROUND AND AIMS: Synthesis of new potential antimicrobial agents and evaluation of their lipophilicity. METHODS: Ten new thiazolyl-oxadiazoline derivatives were synthesized and their structures were validated by 1H-NMR and mass spectrometry. The lipophilicity of the compounds was evaluated using the principal component analysis (PCA) method. The necessary data for applying this method were obtained by reverse-phase thin-layer chromatography (RP-TLC). The antimicrobial activities were tested in vitro against four bacterial strains and one fungal strain. RESULTS: The lipophilicity varied with the structure but could not be correlated with the antimicrobial activity, since this was modest. CONCLUSIONS: We have synthesized ten new heterocyclic compounds. After their physical and chemical characterization, we determined their lipophilicity and screened their antimicrobial activity.