Investigation of Antimicrobial, Anti-Quorum Sensing, and Cytotoxic Activities of Flavonoids Isolated from Pulicaria armena Boiss. & Kotschy ex Boiss. (Asteraceae).

This is the first report on the separation and biological assessment of all metabolites derived from Pulicaria armena (Asteraceae) which is an endemic species narrowly distributed in the eastern part of Turkey. The phytochemical analysis of P. armena resulted in the identification of one simple phenolic glucoside together with eight flavon and flavonol derivatives whose chemical structures were elucidated by NMR experiments and by the comparison of the spectral data with the relevant literature. The screening of all molecules for their antimicrobial, anti-quorum sensing, and cytotoxic activities revealed the biological potential of some of the isolated compounds. Additionally, quorum sensing inhibitory activity of quercetagetin 5,7,3' trimethyl ether was supported by molecular docking studies in the active site of LasR which is the primary regulator of this cell-to-cell communication system in bacteria. Lastly, the critical molecular properties indicating drug-likeness of the compounds isolated from P. armena were predicted. As microbial infections can be a serious problem for cancer patients with compromised immune systems, this comprehensive phytochemical research on P. armena with its anti-quorum sensing and cytotoxic compounds can provide a new approach to the treatment.

Synthesis of Disulfide-Bridged N-Phenyl-N'-(alkyl/aryl/heteroaryl)urea Derivatives and Evaluation of Their Antimicrobial Activities.

The discovery of new antimicrobial agents is extremely needed to overcome multidrug-resistant bacterial and tuberculosis infections. In the present study, eight novel substituted urea derivatives (10a-10h) containing disulfide bond were designed, synthesized and screened for their in vitro antimicrobial activities on standard strains of Gram-positive and Gram-negative bacteria as well as on Mycobacterium tuberculosis. According to the obtained results, antibacterial effects of the compounds were found to be considerably better than their antimycobacterial activities along with their weak cytotoxic effects. Molecular docking studies were performed to gain insights into the antibacterial activity mechanism of the synthesized compounds. The interactions and the orientation of compound 10a (1,1'-((disulfanediylbis(methylene))bis(2,1-phenylene))bis(3-phenylurea)) were found to be highly similar to the original ligand within the binding pocket E. faecalis ß-ketoacyl acyl carrier protein synthase III (FabH). Finally, a theoretical study was established to predict the physicochemical properties of the compounds.