title: Search for Novel Antibacterial Compounds and Targets.
abstract: Drug-resistant bacteria including methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Pseudomonas aeruginosa, and vancomycin-resistant enterococci (VRE) have been spreading; however, the development of new antibacterial drugs has not progressed accordingly. Novel antibacterial drugs or their candidate seeds need to be developed for effective antibiotic therapy. Under these conditions, the search for novel compounds and novel targets is important. In Okayama University, as a part of the Drug Discovery for Intractable Infectious Diseases project, we are proceeding with the development of antibacterial drugs for the treatment of drug-resistant bacterial infections. We found that riccardin C (a natural product of liverwort) and 6,6'-dihydroxythiobinupharidine (from the crude drug Senkotsu) exhibited strong antibacterial activities, particularly against Gram-positive bacteria. We showed that riccardin C induced cell membrane leakage and that 6,6'-dihydroxythiobinupharidine inhibited DNA topoisomerase IV. Moreover, 6,6'-dihydroxythiobinupharidine exerted synergistic effects with already known anti-MRSA drugs as well as with vancomycin for VRE.
authors.affiliation: Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University.
authors.forename: Teruo
authors.initials: T
authors.lastname: Kuroda
authors.forename: Wakano
authors.initials: W
authors.lastname: Ogawa
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001688:Biological Products; D002462:Cell Membrane / Q000378:metabolism; D027101:DNA Topoisomerase IV / Q000037:antagonists & inhibitors; D055808:Drug Discovery; D024901:Drug Resistance, Multiple, Bacterial; D004988:Ethers, Cyclic / Q000494:pharmacology; D035926:Hepatophyta; D007564:Japan; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D065507:Vancomycin-Resistant Enterococci / Q000187:drug effects
chemical_list: D000470:Alkaloids; D000900:Anti-Bacterial Agents; D001688:Biological Products; D004988:Ethers, Cyclic; C505660:riccardin C; C003886:dihydroxythiobinupharidine; D027101:DNA Topoisomerase IV