Novel 2,4-disubstituted quinazoline analogs as antibacterial agents with improved cytotoxicity profile: Modification of the benzenoid part.

Bacterial resistance to currently used antibiotics demands the development of novel antibacterial agents with good safety margins and sufficient efficacy against multi-drug resistant isolates. We have previously described the synthesis of N-butyl-2-(butylthio)quinazolin-4-amine (I) as an optimized hit with broad-spectrum antibacterial activity and low cytotoxicity. In addition, we have identified a potential growing vector for this series of compounds. Herein, we describe further hit optimization which includes systematic diversifications of both the benzenoid part and the substituents at position 6 and 7 of compound I. Growing of the molecule beside the core modifications yielded several compounds with remarkable anti(myco)bacterial activity against a panel of pathogenic bacteria, including drug-resistant strains. Compound 12 showed a 2-4 fold improvement in activity than I against S. aureus Newman, S. pneumoniae DSM-20566 and E. faecalis DSM-20478. The compounds also showed a good safety profile towards human HepG2 cells.

Molecularly Imprinted Solid Phase Extraction Strategy for Quinic Acid.

Quinic acid (QA) and its ester conjugates have been subjected to in-depth scientific investigations for their antioxidant properties. In this study, molecularly imprinted polymers (MIPs) were used for selective extraction of quinic acid (QA) from coffee bean extract. Computational modelling was performed to optimize the process of MIP preparation. Three different functional monomers (allylamine, methacrylic acid (MAA) and 4-vinylpyridine (4-VP)) were tested for imprinting. The ratio of each monomer to template chosen was based on the optimum ratio obtained from computational studies. Equilibrium rebinding studies were conducted and MIP C, which was prepared using 4-VP as functional monomer with template to monomer ratio of 1:5, showed better binding performance than the other prepared MIPs. Accordingly, MIP C was chosen to be applied for selective separation of QA using solid-phase extraction. The selectivity of MIP C towards QA was tested versus its analogues found in coffee (caffeic acid and chlorogenic acid). Molecularly imprinted solid-phase extraction (MISPE) using MIP C as sorbent was then applied for selective extraction of QA from aqueous coffee extract. The applied MISPE was able to retrieve 81.918 ± 3.027% of QA with a significant reduction in the amount of other components in the extract.