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@article{1727182,
author = {Goněc, Tomáš and Malík, Ivan and Csöllei, Jozef and Jampilek, J and Stolarikova, J and Solovic, I and Mikuš, Peter and Keltosova, S and Kollár, Peter and J, O Mahony and Coffey, A},
article_number = {12},
doi = {http://dx.doi.org/10.3390/molecules22122100},
keywords = {N-arylpiperazines; arylaminoethanols; lipophilicity; electronic properties; Mycobacterium tuberculosis H37Rv},
language = {eng},
issn = {1420-3049},
journal = {Molecules},
title = {Synthesis and (In Vitro) Antimycobacterial Activity of Novel N-Arylpiperazines Containing an Ethane-1,2-diyl Connecting Chain},
volume = {22},
year = {2017}
}
TY - JOUR
ID - 1727182
AU - Goněc, Tomáš - Malík, Ivan - Csöllei, Jozef - Jampilek, J - Stolarikova, J - Solovic, I - Mikuš, Peter - Keltosova, S - Kollár, Peter - J, O Mahony - Coffey, A
PY - 2017
TI - Synthesis and (In Vitro) Antimycobacterial Activity of Novel N-Arylpiperazines Containing an Ethane-1,2-diyl Connecting Chain
JF - Molecules
VL - 22
IS - 12
PB - Mayer und Muller
SN - 14203049
KW - N-arylpiperazines
KW - arylaminoethanols
KW - lipophilicity
KW - electronic properties
KW - Mycobacterium tuberculosis H37Rv
N2 - Novel 1-(2-{3-/4-[(alkoxycarbonyl)amino]phenyl}-2-hydroxyethyl)-4-(2-fluorophenyl)-piperazin-1-ium chlorides (alkoxy = methoxy to butoxy; 8a-h) have been designed and synthesized through multistep reactions as a part of on-going research programme focused on finding new antimycobacterials. Lipophilic properties of these compounds were estimated by RP-HPLC using methanol/water mobile phases with a various volume fraction of the organic modifier. The log k(w) values, which were extrapolated from intercepts of a linear relationship between the logarithm of a retention factor k (log k) and volume fraction of a mobile phase modifier (phi(M)), varied from 2.113 (8e) to 2.930 (8h) and indicated relatively high lipophilicity of these salts. Electronic properties of the molecules 8a-h were investigated by evaluation of their UV/Vis spectra. In a next phase of the research, the compounds 8a-h were (in vitro) screened against M. tuberculosis CNCTC My 331/88 (identical with H37Rv and ATCC 2794), M. kansasii CNCTC My 235/80 (identical with ATCC 12478), a M. kansasii 6 509/96 clinical isolate, M. avium CNCTC My 330/80 (identical with ATCC 25291) and M. avium intracellulare ATCC 13950, respectively, as well as against M. kansasii CIT11/06, M. avium subsp. paratuberculosis CIT03 and M. avium hominissuis CIT10/08 clinical isolates using isoniazid, ethambutol, ofloxacin, ciprofloxacin or pyrazinamide as reference drugs. The tested compounds 8a-h were found to be the most promising against M. tuberculosis; a MIC = 8 M was observed for the most effective 1-(2-{4-[(butoxycarbonyl)amino]phenyl}-2-hydroxyethyl)-4-(2-fluorophenyl)piperazin-1-ium chloride (8h). In addition, all of them showed low (insignificant) (in vitro) toxicity against a human monocytic leukemia THP-1 cell line, as observed LD50 values > 30 M indicated. The structure-antimycobacterial activity relationships of the analyzed 8a-h series are also discussed.
ER -
GONĚC, Tomáš, Ivan MALÍK, Jozef CSÖLLEI, J JAMPILEK, J STOLARIKOVA, I SOLOVIC, Peter MIKUŠ, S KELTOSOVA, Peter KOLLÁR, O Mahony J a A COFFEY. Synthesis and (In Vitro) Antimycobacterial Activity of Novel N-Arylpiperazines Containing an Ethane-1,2-diyl Connecting Chain. \textit{Molecules}. Mayer und Muller, 2017, roč.~22, č.~12, 33 s. ISSN~1420-3049. Dostupné z: https://dx.doi.org/10.3390/molecules22122100.
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