-
Something wrong with this record ?
Synthesis and antimycobacterial evaluation of pyrazinamide derivatives with benzylamino substitution
J. Zitko, P. Paterová, V. Kubíček, J. Mandíková, F. Trejtnar, J. Kuneš, M. Doležal,
Language English Country England, Great Britain
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
NT13346
MZ0
CEP Register
- MeSH
- Antitubercular Agents chemical synthesis pharmacology MeSH
- Benzylamines chemistry MeSH
- Inhibitory Concentration 50 MeSH
- Cells, Cultured MeSH
- Humans MeSH
- Microbial Sensitivity Tests MeSH
- Molecular Structure MeSH
- Mycobacterium drug effects MeSH
- Pyrazinamide chemical synthesis pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
A series of 19 new compounds related to pyrazinamide were synthesized, characterized with analytical data and screened for in vitro whole cell antimycobacterial activity against Mycobacterium tuberculosis H37Rv, Mycobacterium kansasii and two types of Mycobacterium avium. The series consisted of 3-(benzylamino)-5-cyanopyrazine-2-carboxamides and 3-(benzylamino)pyrazine-2,5-dicarbonitriles with various substituents on the phenyl ring. RP-HPLC method was used to determine the lipophilicity of the prepared compounds. Nine compounds exerted similar or better activity against Mycobacterium tuberculosis compared to pyrazinamide (MIC=6.25-12.5 μg/mL). 3-(Benzylamino)pyrazine-2,5-dicarbonitrile inhibited all of the tested mycobacterial strains with MIC within the range 12.5-25 μg/mL. Although not the most active, 4-NH(2) substituted compounds possessed the lowest in vitro cytotoxicity (hepatotoxicity), leading to selectivity index SI=5.5 and SI >21.
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc13031777
- 003
- CZ-PrNML
- 005
- 20181212120110.0
- 007
- ta
- 008
- 131002s2013 enk f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1016/j.bmcl.2012.11.052 $2 doi
- 035 __
- $a (PubMed)23237840
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a enk
- 100 1_
- $a Zitko, Jan $u Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, Hradec Králové 500 05, Czech Republic. jan.zitko@faf.cuni.cz $7 xx0230408
- 245 10
- $a Synthesis and antimycobacterial evaluation of pyrazinamide derivatives with benzylamino substitution / $c J. Zitko, P. Paterová, V. Kubíček, J. Mandíková, F. Trejtnar, J. Kuneš, M. Doležal,
- 520 9_
- $a A series of 19 new compounds related to pyrazinamide were synthesized, characterized with analytical data and screened for in vitro whole cell antimycobacterial activity against Mycobacterium tuberculosis H37Rv, Mycobacterium kansasii and two types of Mycobacterium avium. The series consisted of 3-(benzylamino)-5-cyanopyrazine-2-carboxamides and 3-(benzylamino)pyrazine-2,5-dicarbonitriles with various substituents on the phenyl ring. RP-HPLC method was used to determine the lipophilicity of the prepared compounds. Nine compounds exerted similar or better activity against Mycobacterium tuberculosis compared to pyrazinamide (MIC=6.25-12.5 μg/mL). 3-(Benzylamino)pyrazine-2,5-dicarbonitrile inhibited all of the tested mycobacterial strains with MIC within the range 12.5-25 μg/mL. Although not the most active, 4-NH(2) substituted compounds possessed the lowest in vitro cytotoxicity (hepatotoxicity), leading to selectivity index SI=5.5 and SI >21.
- 650 _2
- $a antituberkulotika $x chemická syntéza $x farmakologie $7 D000995
- 650 _2
- $a benzylaminy $x chemie $7 D001596
- 650 _2
- $a kultivované buňky $7 D002478
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a inhibiční koncentrace 50 $7 D020128
- 650 _2
- $a mikrobiální testy citlivosti $7 D008826
- 650 _2
- $a molekulární struktura $7 D015394
- 650 _2
- $a Mycobacterium $x účinky léků $7 D009161
- 650 _2
- $a pyrazinamid $x chemická syntéza $x farmakologie $7 D011718
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Paterová, Pavla $u - $7 xx0138094
- 700 1_
- $a Kubíček, Vladimír $u - $7 _AN062437
- 700 1_
- $a Mandíková, Jana $u - $7 xx0159490
- 700 1_
- $a Trejtnar, František $u - $7 xx0143079
- 700 1_
- $a Kuneš, Jiří, $u - $d 1965- $7 xx0105105
- 700 1_
- $a Doležal, Martin, $u - $d 1961- $7 jn19981000714
- 773 0_
- $w MED00000770 $t Bioorganic & medicinal chemistry letters $x 1464-3405 $g Roč. 23, č. 2 (2013), s. 476-479
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/23237840 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20131002 $b ABA008
- 991 __
- $a 20181212120234 $b ABA008
- 999 __
- $a ok $b bmc $g 995864 $s 830222
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2013 $b 23 $c 2 $d 476-479 $i 1464-3405 $m Bioorganic & medicinal chemistry letters $n Bioorg Med Chem Lett $x MED00000770
- GRA __
- $a NT13346 $p MZ0
- LZP __
- $a Pubmed-20131002
