title: Sulfonyl-polyol N,N-dichloroamines with rapid, broad-spectrum antimicrobial activity.
abstract: The discovery and development of antimicrobial agents that do not give rise to resistance remains an ongoing challenge. Our efforts in this regard continue to reveal new potential therapeutic agents with differing physicochemical properties while retaining the effective N,N-dichloroamine pharmacophore as the key antimicrobial warhead. In this Letter, we disclose agents containing polyol units as a water solubilizing group. These sulfonyl-polyol agents show broad spectrum bactericidal and virucidal activity. These compounds show 1 h MBC's of 16-512 μg/mL against Escherichia coli and 4-256 μg/mL against Staphylococcus aureus at neutral pH, and 1-h IC50's of 4.5-32 μM against Adenovirus 5 and 0.7-3.0 μM against Herpes simplex virus 1. The lead compounds were tested in a tissue culture irritancy assay and showed only minimal irritation at the highest concentrations tested.
authors.affiliation: NovaBay Pharmaceuticals, 5980 Horton Street, Suite 550, Emeryville, CA 94608, United States. Electronic address: tshiau@novabaypharma.com.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Shiau
authors.forename: Eddy
authors.initials: E
authors.lastname: Low
authors.forename: Bum
authors.initials: B
authors.lastname: Kim
authors.forename: Eric D
authors.initials: ED
authors.lastname: Turtle
authors.forename: Charles
authors.initials: C
authors.lastname: Francavilla
authors.forename: Donogh J R
authors.initials: DJ
authors.lastname: O'Mahony
authors.forename: Lisa
authors.initials: L
authors.lastname: Friedman
authors.forename: Louisa
authors.initials: L
authors.lastname: D'Lima
authors.forename: Andreas
authors.initials: A
authors.lastname: Jekle
authors.forename: Dmitri
authors.initials: D
authors.lastname: Debabov
authors.forename: Meghan
authors.initials: M
authors.lastname: Zuck
authors.forename: Nichole J
authors.initials: NJ
authors.lastname: Alvarez
authors.forename: Mark
authors.initials: M
authors.lastname: Anderson
authors.forename: Ramin Ron
authors.initials: RR
authors.lastname: Najafi
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Jain
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008826:Microbial Sensitivity Tests; D011108:Polymers / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000187:drug effects; D014709:Vero Cells
chemical_list: D000588:Amines; D000890:Anti-Infective Agents; D011108:Polymers; C024617:polyol
keywords: Bacteria; Bactericidal; Chloroamines; Conjunctivitis; Virucidal; Virus