Evaluation of a 2-aminoimidazole variant as adjuvant treatment for dermal bacterial infections

G Logan Draughn; C Leigh Allen; Patricia A Routh; Maria R Stone; Kelly R Kirker; Laura Boegli; Ryan M Schuchman; Keith E Linder; Ronald E Baynes; Garth James; Christian Melander; Angela Pollard; John Cavanagh

Evaluation of a 2-aminoimidazole variant as adjuvant treatment for dermal bacterial infections

G Logan Draughn, C Leigh Allen, Patricia A Routh, Maria R Stone, Kelly R Kirker, Laura Boegli, Ryan M Schuchman, Keith E Linder, Ronald E Baynes, Garth James, Christian Melander, Angela Pollard, John Cavanagh

Medicinal Chemistry

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Abstract

2-Aminoimidazole (2-AI)-based compounds have been shown to efficiently disrupt biofilm formation, disperse existing biofilms, and resensitize numerous multidrug-resistant bacteria to antibiotics. Using Pseudomonas aeruginosa and Staphylococcus aureus, we provide initial pharmacological studies regarding the application of a 2-AI as a topical adjuvant for persistent dermal infections. In vitro assays indicated that the 2-AI H10 is nonbactericidal, resensitizes bacteria to antibiotics, does not harm the integument, and promotes wound healing. Furthermore, in vivo application of H10 on swine skin caused no gross abnormalities or immune reactions. Taken together, these results indicate that H10 represents a promising lead dermal adjuvant compound.

Original language	English (US)
Pages (from-to)	153-162
Journal	Drug Design, Development and Therapy
Volume	2017
Issue number	11
State	Published - Jan 11 2017

Keywords

transdermal absorption
antimicrobial activity
skin irritation
synergism
oroidin derivative
drip-flow reactor
ESKAPE pathogens

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title = "Evaluation of a 2-aminoimidazole variant as adjuvant treatment for dermal bacterial infections",

abstract = "2-Aminoimidazole (2-AI)-based compounds have been shown to efficiently disrupt biofilm formation, disperse existing biofilms, and resensitize numerous multidrug-resistant bacteria to antibiotics. Using Pseudomonas aeruginosa and Staphylococcus aureus, we provide initial pharmacological studies regarding the application of a 2-AI as a topical adjuvant for persistent dermal infections. In vitro assays indicated that the 2-AI H10 is nonbactericidal, resensitizes bacteria to antibiotics, does not harm the integument, and promotes wound healing. Furthermore, in vivo application of H10 on swine skin caused no gross abnormalities or immune reactions. Taken together, these results indicate that H10 represents a promising lead dermal adjuvant compound.",

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AU - Draughn, G Logan

AU - Allen, C Leigh

AU - Routh, Patricia A

AU - Stone, Maria R

AU - Kirker, Kelly R

AU - Boegli, Laura

AU - Schuchman, Ryan M

AU - Linder, Keith E

AU - Baynes, Ronald E

AU - James, Garth

AU - Melander, Christian

AU - Pollard, Angela

AU - Cavanagh, John

PY - 2017/1/11

Y1 - 2017/1/11

N2 - 2-Aminoimidazole (2-AI)-based compounds have been shown to efficiently disrupt biofilm formation, disperse existing biofilms, and resensitize numerous multidrug-resistant bacteria to antibiotics. Using Pseudomonas aeruginosa and Staphylococcus aureus, we provide initial pharmacological studies regarding the application of a 2-AI as a topical adjuvant for persistent dermal infections. In vitro assays indicated that the 2-AI H10 is nonbactericidal, resensitizes bacteria to antibiotics, does not harm the integument, and promotes wound healing. Furthermore, in vivo application of H10 on swine skin caused no gross abnormalities or immune reactions. Taken together, these results indicate that H10 represents a promising lead dermal adjuvant compound.

AB - 2-Aminoimidazole (2-AI)-based compounds have been shown to efficiently disrupt biofilm formation, disperse existing biofilms, and resensitize numerous multidrug-resistant bacteria to antibiotics. Using Pseudomonas aeruginosa and Staphylococcus aureus, we provide initial pharmacological studies regarding the application of a 2-AI as a topical adjuvant for persistent dermal infections. In vitro assays indicated that the 2-AI H10 is nonbactericidal, resensitizes bacteria to antibiotics, does not harm the integument, and promotes wound healing. Furthermore, in vivo application of H10 on swine skin caused no gross abnormalities or immune reactions. Taken together, these results indicate that H10 represents a promising lead dermal adjuvant compound.

KW - transdermal absorption

KW - antimicrobial activity

KW - skin irritation

KW - synergism

KW - oroidin derivative

KW - drip-flow reactor

KW - ESKAPE pathogens

M3 - Article

SN - 1177-8881

VL - 2017

SP - 153

EP - 162

JO - Drug Design, Development and Therapy

JF - Drug Design, Development and Therapy

IS - 11

ER -

Evaluation of a 2-aminoimidazole variant as adjuvant treatment for dermal bacterial infections

Abstract

Keywords

UN SDGs

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