title: Divergent Synthesis of Three Classes of Antifungal Amphiphilic Kanamycin Derivatives.
abstract: A concise and novel method for site-selective alkylation of 1,3,6',3″-tetraazidokanamycin has been developed that leads to the divergent synthesis of three classes of kanamycin A derivatives. These new amphiphilic kanamycin derivatives bearing alkyl chains length of 4, 6, 7, 8, 9, 10, 12, 14, and 16 have been tested for their antibacterial and antifungal activities. The antibacterial effect of the synthesized kanamycin derivatives declines or disappears as compared to the original kanamycin A. Several compounds, especially those with octyl chain at O-4″ and/or O-6″ positions on the ring III of kanamycin A, show very strong activity as antifungal agents. In addition, these compounds display no toxicity toward mammalian cells. Finally, computational calculation has revealed possible factors that are responsible for the observed regioselectivity. The simplicity in chemical synthesis and the fungal specific property make the lead compounds ideal candidates for the development of novel antifungal agents.
authors.affiliation: Department of Chemistry and Biochemistry, Utah State University , 0300 Old Main Hill, Logan, Utah 84322-0300, United States.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Chemistry and Biochemistry, Utah State University , 0300 Old Main Hill, Logan, Utah 84322-0300, United States.
authors.forename: Madher N
authors.initials: MN
authors.lastname: Alfindee
authors.affiliation: Department of Chemistry and Biochemistry, Utah State University , 0300 Old Main Hill, Logan, Utah 84322-0300, United States.
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, Utah 84322-0300, United States.
authors.forename: Vincent de Paul Nzuwah
authors.initials: VP
authors.lastname: Nziko
authors.affiliation: Department of Biology, Utah State University , 5305 Old Main Hill, Logan, Utah 84322-5305, United States.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Kawasaki
authors.affiliation: Department of Chemistry and Biochemistry, Utah State University , 0300 Old Main Hill, Logan, Utah 84322-0300, United States.
authors.forename: Xinrui
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Biology, Utah State University , 5305 Old Main Hill, Logan, Utah 84322-5305, United States.
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, Utah 84322-0300, United States.
authors.forename: Cheng-Wei Tom
authors.initials: CT
authors.lastname: Chang
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology; D001231:Aspergillus flavus / Q000187:drug effects; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D004926:Escherichia coli / Q000187:drug effects; D005670:Fusarium / Q000187:drug effects; D007612:Kanamycin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D066244:Proton Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D007612:Kanamycin