title: Synthesis and bioactivity investigation of quinone-based dimeric cationic triazolium amphiphiles selective against resistant fungal and bacterial pathogens.
abstract: A series of synthetic dimeric cationic anthraquinone analogs (CAAs) with potent antimicrobial activities against a broad range of fungi and bacteria were developed. These compounds were prepared in 2-3 steps with high overall yield and possess alkyl chain, azole, quinone, and quaternary ammonium complexes (QACs). In vitro biological evaluations reveal prominent inhibitory activities of lead compounds against several drug-susceptible and drug-resistant fungal and bacterial strains, including MRSA, VRE, Candida albicans and Aspergillus flavus. Mode of action investigation reveals that the synthesized dimeric CAA's can disrupt the membrane integrity of fungi. Computational studies reveal possible designs that can revive the activity of QACs against drug-resistant bacteria. Cytotoxicity assays in SKOV-3, a cancer cell line, show that the lead compounds are selectively toxic to fungi and bacteria over human cells.
authors.affiliation: Department of Chemistry and Biochemistry, Utah State University, 0300 Old Main Hill, Logan, UT 84322-0300, USA.
authors.forename: Jaya P
authors.initials: JP
authors.lastname: Shrestha
authors.affiliation: Department of Chemistry and Biochemistry, Utah State University, 0300 Old Main Hill, Logan, UT 84322-0300, USA.
authors.forename: Coleman
authors.initials: C
authors.lastname: Baker
authors.affiliation: Department of Biology, Utah State University, 5305 Old Main Hill, Logan, UT 84322-5305, USA.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Kawasaki
authors.affiliation: Department of Chemistry and Biochemistry, Utah State University, 0300 Old Main Hill, Logan, UT 84322-0300, USA.
authors.forename: Yagya P
authors.initials: YP
authors.lastname: Subedi
authors.affiliation: Department of Chemistry and Biochemistry, Utah State University, 0300 Old Main Hill, Logan, UT 84322-0300, USA.
authors.forename: Nzuwah Nziko
authors.initials: NN
authors.lastname: Vincent de Paul
authors.affiliation: Department of Biology, Utah State University, 5305 Old Main Hill, Logan, UT 84322-5305, USA.
authors.forename: Jon Y
authors.initials: JY
authors.lastname: Takemoto
authors.affiliation: Department of Chemistry and Biochemistry, Utah State University, 0300 Old Main Hill, Logan, UT 84322-0300, USA. Electronic address: tom.chang@usu.edu.
authors.forename: Cheng-Wei Tom
authors.initials: CT
authors.lastname: Chang
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001393:Azoles; D016227:Benzoquinones / Q000737:chemistry; D045744:Cell Line, Tumor; D015195:Drug Design; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D025141:Drug Resistance, Fungal / Q000187:drug effects; D006801:Humans; D012680:Sensitivity and Specificity; D013501:Surface-Active Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D001393:Azoles; D016227:Benzoquinones; D013501:Surface-Active Agents; D014230:Triazoles; C004532:quinone
keywords: 1,4-Naphthoquinone analogs; Cationic anthraquinone analogs; MRSA; Multi-cationic; Quaternary ammonium compound; Triazole antibiotics