Dibasic Derivatives of Phenylcarbamic Acid against Mycobacterial Strains: Old Drugs and New Tricks?

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F71009396%3A_____%2F18%3AN0000032" target="_blank" >RIV/71009396:_____/18:N0000032 - isvavai.cz</a>

Alternative codes found

RIV/86652079:_____/18:00494503 RIV/62157124:16170/18:43877064 RIV/62157124:16370/18:43877064

Result on the web

<a href="https://www.mdpi.com/1420-3049/23/10/2493/htm" target="_blank" >https://www.mdpi.com/1420-3049/23/10/2493/htm</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/molecules23102493" target="_blank" >10.3390/molecules23102493</a>

Result language

angličtina

Original language name

Dibasic Derivatives of Phenylcarbamic Acid against Mycobacterial Strains: Old Drugs and New Tricks?

Original language description

In order to provide a more detailed view on the structure-antimycobacterial activity relationship (SAR) of phenylcarbamic acid derivatives containing two centers of protonation, 1-[2-({[2-/3-(alkoxy)phenyl]amino}carbonyl)oxy]-3-(dipropylammonio)propyl]pyrrolidinium oxalates (1a-d)/dichlorides (1e-h) as well as 1-[2-[({[2-/3-(alkoxy) phenyl] amino} carbonyl) oxy]-3-(dipropylammonio) propyl] azepanium oxalates (1i-l)/dichlorides (1m-p; alkoxy = butoxy to heptyloxy) were physicochemically characterized by estimation of their surface tension (gamma; Traube's stalagmometric method), electronic features (log epsilon; UV/Vis spectrophotometry) and lipophilic propertes (log k(w); isocratic RP-HPLC) as well. The experimental log k(w) dataset was studied together with computational logarithms of partition coefficients (log P) generated by various methods based mainly on atomic or combined atomic and fragmental principles. Similarities and differences between the experimental and in silico lipophilicity descriptors were analyzed by unscaled principal component analysis (PCA). The in vitro activity of compounds 1a-p was inspected against Mycobacterium tuberculosis CNCTC My 331/88 (identical with H37Rv and ATCC 2794, respectively), M. tuberculosis H37Ra ATCC 25177, M. kansasii CNCTC My 235/80 (identical with ATCC 12478), the M. kansasii 6509/96 clinical isolate, M. kansasii DSM 44162, M. avium CNCTC My 330/80 (identical with ATCC 25291), M. smegmatis ATCC 700084 and M. marinum CAMP 5644, respectively. In vitro susceptibility of the mycobacteria to reference drugs isoniazid, ethambutol, ofloxacin or ciprofloxacin was tested as well. A very unique aspect of the research was that many compounds from the set 1a-p were highly efficient almost against all tested mycobacteria. The most promising derivatives showed MIC values varied from 1.9 mu M to 8 mu M, which were lower compared to those of used standards, especially if concerning ability to fight M. tuberculosis H37Ra ATCC 25177, M. kansasii DSM 44162 or M. avium CNCTC My 330/80. Current in vitro biological assays and systematic SAR studies based on PCA approach as well as fitting procedures, which were supported by relevant statistical descriptors, proved that the compounds 1a-p represented a very promising molecular framework for development of 'non-traditional' but effective antimycobacterial agents.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

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Continuities

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

MOLECULES

ISSN

1420-3049

e-ISSN

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Volume of the periodical

23

Issue of the periodical within the volume

10

Country of publishing house

CH - SWITZERLAND

Number of pages

37

Pages from-to

1-37

UT code for WoS article

000451201400089

EID of the result in the Scopus database

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