TY - JOUR
T1 - Addition of ethylamines to the phenols of bithionol and synthetic retinoids does not elicit activity in gram-negative bacteria
AU - Cheng, Ana V.
AU - Schrank, Cassandra L.
AU - Escobar, Iliana E.
AU - Mylonakis, Eleftherios
AU - Wuest, William M.
N1 - Funding Information:
This work was funded by the National Institute of General Medical Sciences ( GM119426 ) and the Georgia Research Alliance based in Atlanta, Georgia to W.M.W., and by National Institutes of Health grant P01 AI083214 to E.M. The NMR instruments used in this work were supported by the National Science Foundation (CHE1531620).
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/5/1
Y1 - 2020/5/1
N2 - Our labs have demonstrated the activity of bithionol and synthetic retinoids against methicillin-resistant Staphylococcus aureus (MRSA), as well as their membrane-acting mechanism of action. However, the compounds lack activity in gram-negative species. Herein, we apply a known strategy for converting gram-positive agents into broad-spectrum therapies: addition of an alkylamine. By appending an alkylamine to the phenols of these known membrane disruptors, we test whether this approach is applicable to our compounds. Ultimately, biological testing in four MRSA strains and three gram-negative species showed abolished or diminished activity in all our analogs compared to their parent compounds and no gram-negative activity. Thus, we find that alkylamines would not elicit broad-spectrum activity from bithionol or CD437 derivatives.
AB - Our labs have demonstrated the activity of bithionol and synthetic retinoids against methicillin-resistant Staphylococcus aureus (MRSA), as well as their membrane-acting mechanism of action. However, the compounds lack activity in gram-negative species. Herein, we apply a known strategy for converting gram-positive agents into broad-spectrum therapies: addition of an alkylamine. By appending an alkylamine to the phenols of these known membrane disruptors, we test whether this approach is applicable to our compounds. Ultimately, biological testing in four MRSA strains and three gram-negative species showed abolished or diminished activity in all our analogs compared to their parent compounds and no gram-negative activity. Thus, we find that alkylamines would not elicit broad-spectrum activity from bithionol or CD437 derivatives.
KW - Bithionol
KW - CD437
KW - Gram-negative bacteria
KW - Methicillin-resistant Staphylococcus aureus
KW - Retinoid
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U2 - 10.1016/j.bmcl.2020.127099
DO - 10.1016/j.bmcl.2020.127099
M3 - Article
C2 - 32171615
AN - SCOPUS:85081935903
VL - 30
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 9
M1 - 127099
ER -