Open AccessPyrazolyl Thioureas and Carbothioamides with an NNSN Motif against MSSA and MRSA
Author(s) -
Anjana Delpe-Acharige,
Man Zhang,
Kayla Eschliman,
Alex G. Dalecki,
Obdulia CovarrubiasZambrano,
Azriel Minjarez-Almeida,
Tejaswi Shrestha,
Tanji Lewis,
Fatimah Alibrahim,
Sophia Leonard,
Riana Roberts,
Anteneh Tebeje,
Aruni P. Malalasekera,
Hongwang Wang,
Madumali Kalubowilage,
Frank Wolschendorf,
Olaf Kutsch,
Stefan H. Bossmann
Publication year - 2021
Publication title -
acs omega
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.779
H-Index - 40
ISSN - 2470-1343
DOI - 10.1021/acsomega.0c04513
Subject(s) - staphylococcus aureus , copper , chemistry , microbiology and biotechnology , stereocenter , strain (injury) , drug , pharmacology , medicine , biology , bacteria , biochemistry , genetics , organic chemistry , enantioselective synthesis , catalysis
A novel series of copper-activatable drugs intended for use against methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) were synthesized, characterized, and tested against the MSSA strain Newman and the MRSA Lac strain (a USA300 strain), respectively. These drugs feature an NNSN structural motif, which enables the binding of copper. In the absence of copper, no activity against MSSA and MRSA at realistic drug concentrations was observed. Although none of the novel drug candidates exhibits a stereocenter, sub-micromolar activities against SA Newman and micromolar activities against SA Lac were observed in the presence, but not in the absence, of bioavailable copper. Copper influx is a component of cellular response to bacterial infections, which is often described as nutritional immunity.