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 β-ketoacyl acyl carrier protein synthase III (FabH). Finally, a theoretical study was established to predict the physicochemical properties of the compounds.
['Dilem Doğan|Şengül|Ş|', 'Buran|Sümeyye|S|', 'Gözde Gündüz|Miyase|M|http://orcid.org/0000-0002-2287-9509', 'Özkul|Ceren|C|', 'Siva Krishna|Vagolu|V|', 'Sriram|Dharmarajan|D|']
D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase D000818:Animals D000900:Anti-Bacterial Agents D000995:Antitubercular Agents D001665:Binding Sites D002470:Cell Survival D004220:Disulfides D013293:Enterococcus faecalis D006090:Gram-Negative Bacteria D006094:Gram-Positive Bacteria D051379:Mice D008826:Microbial Sensitivity Tests D062105:Molecular Docking Simulation D017434:Protein Structure, Tertiary D000067996:RAW 264.7 Cells D013329:Structure-Activity Relationship D014508:Urea
synthesis urea antibacterial activity dimerization drug design