dc.contributor.author |
Pugachev M. |
|
dc.contributor.author |
Shtyrlin N. |
|
dc.contributor.author |
Sapozhnikov S. |
|
dc.contributor.author |
Sysoeva L. |
|
dc.contributor.author |
Iksanova A. |
|
dc.contributor.author |
Nikitina E. |
|
dc.contributor.author |
Musin R. |
|
dc.contributor.author |
Lodochnikova O. |
|
dc.contributor.author |
Berdnikov E. |
|
dc.contributor.author |
Shtyrlin Y. |
|
dc.date.accessioned |
2018-09-18T20:12:03Z |
|
dc.date.available |
2018-09-18T20:12:03Z |
|
dc.date.issued |
2013 |
|
dc.identifier.issn |
0968-0896 |
|
dc.identifier.uri |
https://dspace.kpfu.ru/xmlui/handle/net/137500 |
|
dc.description.abstract |
A series of 23 novel bis-phosphonium salts based on pyridoxine were synthesized and their antibacterial activities were evaluated in vitro. All compounds were inactive against gram-negative bacteria and exhibited the structure-dependent activity against gram-positive bacteria. The antibacterial activity enhanced with the increase in chain length at acetal carbon atom in the order n-Pr > Et > Me. Further increasing of length and branching of alkyl chain leads to the reduction of antibacterial activity. Replacement of the phenyl substituents at the phosphorus atoms in 5,6- bis(triphenylphosphonio(methyl))-2,2,8-trimethyl-4H-[1,3]-dioxino[4,5-c] pyridine dichloride (compound 1) with n-butyl, m-tolyl or p-tolyl as well as chloride anions in the compound 1 with bromides (compound 14a) increased the activity against Staphylococcus aureus and Staphylococcus epidermidis up to 5 times (MICs = 1-1.25 μg/ml). But in practically all cases chemical modifications of compound 1 led to the increase of its toxicity for HEK-293 cells. The only exception is compound 5,6-bis[tributylphosphonio(methyl)]-2,2,8- trimethyl-4H-[1,3]dioxino[4,5-c]pyridine dichloride (10a) which demonstrated lower MIC values against S. aureus and S. epidermidis (1 μg/ml) and lower cytotoxicity on HEK-293 cells (CC50 = 200 μg/ml). Compound 10a had no significant mutagenic and genotoxic effects and was selected for further evaluation. It should be noted that all bis-phosphonium salt based on pyridoxine were much more toxic than vancomycin. © 2013 Elsevier Ltd. All rights reserved. |
|
dc.relation.ispartofseries |
Bioorganic and Medicinal Chemistry |
|
dc.subject |
Antibacterial activity |
|
dc.subject |
Lipophilicity |
|
dc.subject |
Pyridoxine |
|
dc.subject |
Quaternary phosphonium salts |
|
dc.subject |
Structure-activity relationship |
|
dc.title |
Bis-phosphonium salts of pyridoxine: The relationship between structure and antibacterial activity |
|
dc.type |
Article |
|
dc.relation.ispartofseries-issue |
23 |
|
dc.relation.ispartofseries-volume |
21 |
|
dc.collection |
Публикации сотрудников КФУ |
|
dc.relation.startpage |
7330 |
|
dc.source.id |
SCOPUS09680896-2013-21-23-SID84886954100 |
|