TY - JOUR
T1 - Mannich Ketones as Possible Antimycobacterial Agents
AU - Lutz, Zsolt
AU - Orbán, Katalin
AU - Bóna, Ágnes
AU - Márk, László
AU - Maász, Gábor
AU - Prókai, László
AU - Seress, Lázló
AU - Lóránd, Tamás
N1 - Funding Information:
This study was financed by the the research grant GINOP-2.3.2-15-2016-00049 and GINOP-2.3.3-15-2016-00025. L.P. was supported by The Welch Foundation (endowment BK-0031). Z.L. is grateful to Judit Misley for the preparation and the ruthenium red cytochemical staining of our electron microscopic preparations. We thank Krisztina Sajti for her technical assistance. The present scientific contribution is dedicated to the 650th anniversary of the foundation of the University of Pécs, Hungary. This statement is to certify that all authors have seen and approved the manuscript being submitted. We warrant that the article is the authors’ original work. We warrant that the article has not received prior publication and is not under consideration for publication elsewhere. On behalf of all co-authors, the corresponding author shall bear full responsibility for the submission. This research has not been submitted for publication nor has it been published in whole or in part elsewhere. We attest to the fact that all authors listed on the title page have contributed significantly to the work, have read the manuscript, attest to the validity and legitimacy of the data and its interpretation, and agree to its submission to the journal Archiv der Pharmazie.
Publisher Copyright:
© 2017 Deutsche Pharmazeutische Gesellschaft
PY - 2017/9
Y1 - 2017/9
N2 - Twenty-three known unsaturated and fused Mannich ketones and their reduced derivatives (amino alcohols) were selected for an antituberculotic study. They were screened against several mycobacterial strains including Mycobacterium tuberculosis, M. xenopi, and M. gordonae, and minimum inhibitory concentration values were also determined using the standard antituberculotic drug isoniazid (INH) as a reference. Structure–activity relationships were also studied. The mode of action of the test compounds was investigated using transmission electron microscopy, high-performance liquid chromatography, and matrix-assisted desorption/ionization mass spectrometry. Several test substances proved to be as potent as INH, but their antimycobacterial spectra were broader than that of INH. Our findings suggest that their mode of action is probably through the inhibition of mycobacterial cell wall biosynthesis.
AB - Twenty-three known unsaturated and fused Mannich ketones and their reduced derivatives (amino alcohols) were selected for an antituberculotic study. They were screened against several mycobacterial strains including Mycobacterium tuberculosis, M. xenopi, and M. gordonae, and minimum inhibitory concentration values were also determined using the standard antituberculotic drug isoniazid (INH) as a reference. Structure–activity relationships were also studied. The mode of action of the test compounds was investigated using transmission electron microscopy, high-performance liquid chromatography, and matrix-assisted desorption/ionization mass spectrometry. Several test substances proved to be as potent as INH, but their antimycobacterial spectra were broader than that of INH. Our findings suggest that their mode of action is probably through the inhibition of mycobacterial cell wall biosynthesis.
KW - Antimycobacterial activity
KW - Antituberculosis activity
KW - Atypical mycobacteria
UR - http://www.scopus.com/inward/record.url?scp=85026418458&partnerID=8YFLogxK
U2 - 10.1002/ardp.201700102
DO - 10.1002/ardp.201700102
M3 - Article
C2 - 28752666
AN - SCOPUS:85026418458
SN - 0365-6233
VL - 350
JO - Archiv der Pharmazie
JF - Archiv der Pharmazie
IS - 9
M1 - 1700102
ER -