title: Structure-activity relationships for antibacterial to antifungal conversion of kanamycin to amphiphilic analogues.
abstract: Novel fungicides are urgently needed. It was recently reported that the attachment of an octyl group at the O-4″ position of kanamycin B converts this antibacterial aminoglycoside into a novel antifungal agent. To elucidate the structure-activity relationship (SAR) for this phenomenon, a lead compound FG03 with a hydroxyl group replacing the 3″-NH2 group of kanamycin B was synthesized. FG03's antifungal activity and synthetic scheme inspired the synthesis of a library of kanamycin B analogues alkylated at various hydroxyl groups. SAR studies of the library revealed that for antifungal activity the O-4″ position is the optimal site for attaching a linear alkyl chain and that the 3″-NH2 and 6″-OH groups of the kanamycin B parent molecule are not essential for antifungal activity. The discovery of lead compound, FG03, is an example of reviving clinically obsolete drugs like kanamycin by simple chemical modification and an alternative strategy for discovering novel antimicrobials.
authors.affiliation: †Department of Chemistry and Biochemistry, Utah State University, 0300 Old Main Hill, Logan, Utah 84322-0300, United States.
authors.forename: Marina
authors.initials: M
authors.lastname: Fosso
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: 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: Vincent de Paul Nzuwah
authors.initials: Vde P
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 Biology, Utah State University, 5305 Old Main Hill, Logan, Utah 84322-5305, United States.
authors.forename: Sanjib K
authors.initials: SK
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: Jeremiah
authors.initials: J
authors.lastname: Bearss
authors.affiliation: †Department of Chemistry and Biochemistry, Utah State University, 0300 Old Main Hill, Logan, Utah 84322-0300, United States.
authors.forename: Rylee
authors.initials: R
authors.lastname: Gregory
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: CW
authors.lastname: Chang
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D055808:Drug Discovery; D007612:Kanamycin / Q000737:chemistry*; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship; D013501:Surface-Active Agents / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D013501:Surface-Active Agents; D007612:Kanamycin