title: Antibacterial activity of substituted 5-methylbenzo[c]phenanthridinium derivatives.
abstract: Antibiotic resistance has prompted efforts to discover antibiotics with novel mechanisms of action. FtsZ is an essential protein for bacterial cell division, and has been viewed as an attractive target for the development of new antibiotics. Sanguinarine is a benzophenanthridine alkaloid that prevents cytokinesis in bacteria by inhibiting FtsZ self-assembly. In this study, a series of 5-methylbenzo[c]phenanthridinium derivatives were synthesized and evaluated for antibacterial activity against Staphylococcus aureus and Enterococcus faecalis. The data indicate that the presence of a 1- or 12-phenyl substituent on 2,3,8,9-tetramethoxy-5-methylbenzo[c]phenanthridinium chloride significantly enhances antibacterial activity relative to the parent compound or sanguinarine.
authors.affiliation: TAXIS Pharmaceuticals Inc., North Brunswick, NJ 08902, USA.
authors.forename: Ajit
authors.initials: A
authors.lastname: Parhi
authors.forename: Cody
authors.initials: C
authors.lastname: Kelley
authors.forename: Malvika
authors.initials: M
authors.lastname: Kaul
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Pilch
authors.forename: Edmond J
authors.initials: EJ
authors.lastname: LaVoie
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D053119:Benzophenanthridines / Q000737:chemistry / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013293:Enterococcus faecalis / Q000187:drug effects*; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D010617:Phenanthridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D053119:Benzophenanthridines; D003598:Cytoskeletal Proteins; C071525:FtsZ protein, Bacteria; D007546:Isoquinolines; D010617:Phenanthridines; C014740:phenanthridinium; C005705:sanguinarine