-
Je něco špatně v tomto záznamu ?
Design, Synthesis, Antimycobacterial Evaluation, and In Silico Studies of 3-(Phenylcarbamoyl)-pyrazine-2-carboxylic Acids
L. Semelková, P. Janošcová, C. Fernandes, G. Bouz, O. Janďourek, K. Konečná, P. Paterová, L. Navrátilová, J. Kuneš, M. Doležal, J. Zitko,
Jazyk angličtina Země Švýcarsko
Typ dokumentu časopisecké články
Free Medical Journals od 1997
PubMed Central od 2001
Europe PubMed Central od 2001
ProQuest Central od 1997-01-01
Open Access Digital Library od 1997-01-01
Medline Complete (EBSCOhost) od 2009-03-01
Health & Medicine (ProQuest) od 1997-01-01
Odkazy
PubMed
28880230
DOI
10.3390/molecules22091491
Knihovny.cz E-zdroje
- MeSH
- alkoholoxidoreduktasy antagonisté a inhibitory chemie MeSH
- antibakteriální látky chemie farmakologie MeSH
- antifungální látky chemie farmakologie MeSH
- bakteriální proteiny antagonisté a inhibitory chemie MeSH
- lidé MeSH
- mikrobiální testy citlivosti metody MeSH
- molekulární struktura MeSH
- Mycobacterium tuberculosis účinky léků MeSH
- počítačová simulace MeSH
- pyraziny chemie farmakologie MeSH
- racionální návrh léčiv MeSH
- simulace molekulového dockingu metody MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Pyrazinamide, the first-line antitubercular drug, has been regarded the basic component of tuberculosis treatment for over sixty years. Researchers have investigated its effect on Mycobacterium tuberculosis for this long time, and as a result, new potential targets of pyrazinamide or its active form, pyrazinoic acid, have been found. We have designed and prepared 3-(phenyl-carbamoyl)pyrazine-2-carboxylic acids as more lipophilic derivatives of pyrazinoic acid. We also prepared methyl and propyl derivatives as prodrugs with further increased lipophilicity. Antimycobacterial, antibacterial and antifungal growth inhibiting activity was investigated in all prepared compounds. 3-[(4-Nitrophenyl)carbamoyl]pyrazine-2-carboxylic acid (16) exerted high antimycobacterial activity against Mycobacterium tuberculosis H37Rv with MIC = 1.56 μg·mL-1 (5 μM). Propyl 3-{[4-(trifluoromethyl)phenyl]carbamoyl}pyrazine-2-carboxylate (18a) showed also high antimycobacterial activity against Mycobacterium tuberculosis H37Rv with MIC = 3.13 μg·mL-1. In vitro cytotoxicity of the active compounds was investigated and no significant cytotoxic effect was observed. Based to structural similarity to known inhibitors of decaprenylphosphoryl-β-d-ribose oxidase, DprE1, we performed molecular docking of the prepared acids to DprE1. These in silico experiments indicate that modification of the linker connecting aromatic parts of molecule does not have any negative influence on the binding.
- 000
- 00000naa a2200000 a 4500
- 001
- bmc18033737
- 003
- CZ-PrNML
- 005
- 20240528081109.0
- 007
- ta
- 008
- 181008s2017 sz f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.3390/molecules22091491 $2 doi
- 035 __
- $a (PubMed)28880230
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a sz
- 100 1_
- $a Semelková, Lucia $u Faculty of Pharmacy in Hradec Králové, Charles University, Heyrovského 1203, Hradec Králové 500 05, Czech Republic. semelkol@faf.cuni.cz.
- 245 10
- $a Design, Synthesis, Antimycobacterial Evaluation, and In Silico Studies of 3-(Phenylcarbamoyl)-pyrazine-2-carboxylic Acids / $c L. Semelková, P. Janošcová, C. Fernandes, G. Bouz, O. Janďourek, K. Konečná, P. Paterová, L. Navrátilová, J. Kuneš, M. Doležal, J. Zitko,
- 520 9_
- $a Pyrazinamide, the first-line antitubercular drug, has been regarded the basic component of tuberculosis treatment for over sixty years. Researchers have investigated its effect on Mycobacterium tuberculosis for this long time, and as a result, new potential targets of pyrazinamide or its active form, pyrazinoic acid, have been found. We have designed and prepared 3-(phenyl-carbamoyl)pyrazine-2-carboxylic acids as more lipophilic derivatives of pyrazinoic acid. We also prepared methyl and propyl derivatives as prodrugs with further increased lipophilicity. Antimycobacterial, antibacterial and antifungal growth inhibiting activity was investigated in all prepared compounds. 3-[(4-Nitrophenyl)carbamoyl]pyrazine-2-carboxylic acid (16) exerted high antimycobacterial activity against Mycobacterium tuberculosis H37Rv with MIC = 1.56 μg·mL-1 (5 μM). Propyl 3-{[4-(trifluoromethyl)phenyl]carbamoyl}pyrazine-2-carboxylate (18a) showed also high antimycobacterial activity against Mycobacterium tuberculosis H37Rv with MIC = 3.13 μg·mL-1. In vitro cytotoxicity of the active compounds was investigated and no significant cytotoxic effect was observed. Based to structural similarity to known inhibitors of decaprenylphosphoryl-β-d-ribose oxidase, DprE1, we performed molecular docking of the prepared acids to DprE1. These in silico experiments indicate that modification of the linker connecting aromatic parts of molecule does not have any negative influence on the binding.
- 650 _2
- $a alkoholoxidoreduktasy $x antagonisté a inhibitory $x chemie $7 D000429
- 650 _2
- $a antibakteriální látky $x chemie $x farmakologie $7 D000900
- 650 _2
- $a antifungální látky $x chemie $x farmakologie $7 D000935
- 650 _2
- $a bakteriální proteiny $x antagonisté a inhibitory $x chemie $7 D001426
- 650 _2
- $a počítačová simulace $7 D003198
- 650 _2
- $a racionální návrh léčiv $7 D015195
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a mikrobiální testy citlivosti $x metody $7 D008826
- 650 _2
- $a simulace molekulového dockingu $x metody $7 D062105
- 650 _2
- $a molekulární struktura $7 D015394
- 650 _2
- $a Mycobacterium tuberculosis $x účinky léků $7 D009169
- 650 _2
- $a pyraziny $x chemie $x farmakologie $7 D011719
- 650 _2
- $a vztahy mezi strukturou a aktivitou $7 D013329
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Janošcová, Petra $u Faculty of Pharmacy in Hradec Králové, Charles University, Heyrovského 1203, Hradec Králové 500 05, Czech Republic. Petra.Janoscova@seznam.cz.
- 700 1_
- $a Fernandes, Carlos $u Faculty of Pharmacy in Hradec Králové, Charles University, Heyrovského 1203, Hradec Králové 500 05, Czech Republic. oaksdonsad@gmail.com.
- 700 1_
- $a Bouz, Ghada $u Faculty of Pharmacy in Hradec Králové, Charles University, Heyrovského 1203, Hradec Králové 500 05, Czech Republic. bouzg@faf.cuni.cz.
- 700 1_
- $a Janďourek, Ondřej $u Faculty of Pharmacy in Hradec Králové, Charles University, Heyrovského 1203, Hradec Králové 500 05, Czech Republic. JANDO6AA@faf.cuni.cz.
- 700 1_
- $a Konečná, Klára $u Faculty of Pharmacy in Hradec Králové, Charles University, Heyrovského 1203, Hradec Králové 500 05, Czech Republic. konecna@faf.cuni.cz.
- 700 1_
- $a Paterová, Pavla $u Department of Clinical Microbiology, University Hospital, Sokolská 581, Hradec Králové 500 05, Czech Republic. pavla.paterova@fnhk.cz.
- 700 1_
- $a Navrátilová, Lucie $u Faculty of Pharmacy in Hradec Králové, Charles University, Heyrovského 1203, Hradec Králové 500 05, Czech Republic. navratl2@faf.cuni.cz.
- 700 1_
- $a Kuneš, Jiří $u Faculty of Pharmacy in Hradec Králové, Charles University, Heyrovského 1203, Hradec Králové 500 05, Czech Republic. kunes@faf.cuni.cz.
- 700 1_
- $a Doležal, Martin, $d 1961- $u Faculty of Pharmacy in Hradec Králové, Charles University, Heyrovského 1203, Hradec Králové 500 05, Czech Republic. dolezalm@faf.cuni.cz. $7 jn19981000714
- 700 1_
- $a Zitko, Jan $u Faculty of Pharmacy in Hradec Králové, Charles University, Heyrovského 1203, Hradec Králové 500 05, Czech Republic. jan.zitko@faf.cuni.cz.
- 773 0_
- $w MED00180394 $t Molecules $x 1420-3049 $g Roč. 22, č. 9 (2017)
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/28880230 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20181008 $b ABA008
- 991 __
- $a 20240528081106 $b ABA008
- 999 __
- $a ok $b bmc $g 1340974 $s 1030731
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2017 $b 22 $c 9 $e 20170907 $i 1420-3049 $m Molecules $n Molecules $x MED00180394
- LZP __
- $a Pubmed-20181008