Synthesis and Critical View on the Structure-Activity Relationships of N-(Substituted phenyl)-/N-Diphenylmethyl-piperazine-Based Conjugates as Antimycobacterial Agents
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14160%2F21%3A00124261" target="_blank" >RIV/00216224:14160/21:00124261 - isvavai.cz</a>
Result on the web
<a href="https://www.mdpi.com/2076-3417/12/1/300" target="_blank" >https://www.mdpi.com/2076-3417/12/1/300</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/app12010300" target="_blank" >10.3390/app12010300</a>
Alternative languages
Result language
angličtina
Original language name
Synthesis and Critical View on the Structure-Activity Relationships of N-(Substituted phenyl)-/N-Diphenylmethyl-piperazine-Based Conjugates as Antimycobacterial Agents
Original language description
This research focused on a three-step synthesis, analytical, physicochemical, and biological evaluation of hybrid molecules 6a-g, containing a lipophilic 3-trifluoromethylphenyl moiety, polar carbamoyloxy bridge, 2-hydroxypropan-1,3-diyl chain and 4-(substituted phenyl)-/4-diphenylmethylpiperazin-1-ium-1-yl fragment. The estimation of analytical and physicochemical descriptors (m/z(measured) via HPLC-UV/HR-MS, log epsilon(2 (Ch-T)) from UV/Vis spectrophotometry and log k(w) via RP-HPLC) as well as in vitro antimycobacterial and cytotoxic screening of given compounds were carried out (i.e., determination of MIC and IC50 values). These highly lipophilic molecules (log k(w) = 4.1170-5.2184) were tested against Mycobacterium tuberculosis H37Ra ATCC 25177 (Mtb H37Ra), M. kansasii DSM 44162 (MK), M. smegmatis ATCC 700084 (MS), and M. marinum CAMP 5644 (MM). The impact of the 6a-g set on the viability of human liver hepatocellular carcinoma (HepG2) cells was also investigated. 1-[2-Hydroxypropyl-{(3-trifluoromethyl)- phenyl}carbamoyloxy]-4-(3,4-dichlorophenyl)piperazin-1-ium chloride (6e) and 1-[2-hydroxy- propyl-{(3-trifluoromethyl)phenyl}carbamoyloxy]-4-(4-diphenylmethyl)piperazin-1-ium chloride (6g) most effectively inhibited the growth of Mtb H37Ra (MIC < 3.80 mu M). The substance 6g also showed interesting activity against MM (MIC = 8.09 mu M). All obtained data served as input values for structure-activity relationship evaluations using statistical principal component analysis. In fact, the toxicity of both 6e (IC50 = 29.39 mu M) and 6g (IC50 = 22.18 mu M) in HepG2 cells as well as selectivity index (SI) values (SI < 10.00) prevented to consider these promising antimycobacterials safe.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30107 - Medicinal chemistry
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Applied sciences
ISSN
2076-3417
e-ISSN
2076-3417
Volume of the periodical
12
Issue of the periodical within the volume
1
Country of publishing house
CH - SWITZERLAND
Number of pages
20
Pages from-to
1-20
UT code for WoS article
000752599900001
EID of the result in the Scopus database
2-s2.0-85122024992