title: [New amides of phenazine-1-carboxylic acid: antimicrobial activity and structure-activity relationship].
abstract: Complex investigation of new phenazine-1-carboxylic acid (PCA-1) phenylamides allowed to reveal their ability for substantial growth retardation of three gram-positive bacterial strains--Micrococcus sp., Erysipelothrix rhusiopathiae and Staphylococcus aureus. The strong inhibitory activity of PCA-1 derivatives towards the RNA synthesis in in vitro T7-RNA-polymerase transcription system was also shown, and this property depended on concentration and structure of the tested compounds. The methods of computer modeling outlined the possible mechanism of RNA synthesis inhibition by PCA-1 amides: this process is arisen due to formation of stable complex of substances with enzyme at the position of substrate (rNTP) binding site. The revealed accordance of suppressor PCA-1 amides action in the enzymatic transcription system with antibacterial activity of these agents allows assuming that DNA-dependent RNA polymerase might be one of the cellular targets for tested bacteria. Such an approach permits to propose the use of such in vitro transcription model system to reveal biologically active substances among newly synthesized compounds, having close action mechanism.
authors.forename: L H
authors.initials: LH
authors.lastname: Pal'chykovs'ka
authors.forename: I V
authors.initials: IV
authors.lastname: Aleksieieva
authors.forename: V H
authors.initials: VH
authors.lastname: Kostina
authors.forename: M O
authors.initials: MO
authors.lastname: Platonov
authors.forename: V V
authors.initials: VV
authors.lastname: Nehruts'ka
authors.forename: O M
authors.initials: OM
authors.lastname: Deriabin
authors.forename: O A
authors.initials: OA
authors.lastname: Tarasov
authors.forename: A D
authors.initials: AD
authors.lastname: Shved
mesh_terms: D000577:Amides / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D010619:Phenazines / Q000737:chemistry; D012329:RNA, Bacterial / Q000096:biosynthesis; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D000577:Amides; D000900:Anti-Bacterial Agents; D010619:Phenazines; D012329:RNA, Bacterial; C037165:1-phenazinecarboxylic acid