Antibacterial and antifungal activity of acyclic and macrocyclic uracil derivatives with quaternized nitrogen atoms in spacers.
The reactions of 1,3-bis(alpha,omega-bromoalkyl)-6-methyluracils with 1,3-bis(alpha,omega-ethylaminoalkyl)-6-methyluracils or 1,3-bis(bromopentyl)thymine with butylamine afforded pyrimidinophanes containing one or two uracil units and nitrogen atoms in bridging polymethylene chains. In some cases individual geometric isomers of pyrimidinophanes differing in the mutual arrangement of the carbonyl and methyl groups at different pyrimidine rings were isolated. Quaternization of the bridging nitrogen atom with o-nitrobenzyl bromide, benzyl bromide, n-decyl bromide gave rise to water-soluble pyrimidinophanes which were evaluated for their antibacterial and antifungal activity. The arrangement of the carbonyl groups in macrocycles doesn't affect the activity. Antibacterial and antifungal activity of pyrimidinophanes increases with the increase of polymethylene N(pyr)-N-chain length and dramatically increases upon the introduction of n-decyl substituent at nitrogen atoms in spacers. Pyrimidinophanes with 5 and 6 methylene groups in N(pyr)-N-chain and n-decyl substituent showed significant bacteriostatic, fungistatic, bactericidal, fungicidal activity which comparable with standard antibacterial and antifungal drugs. Acyclic counterpart demonstrated the highest activity against fungi. Toxicity of more effective pyrimidinophanes was determined for mice and Daphnia magna Straus.
Semenov
V E
VE
A.E. Arbuzov Institute of Organic and Physical Chemistry of the Russian Academy of Sciences, Kazan, 420088, Arbuzov str. 8, Russian Federation. sve@iopc.kcn.ru
Voloshina
A D
AD
Toroptzova
E M
EM
Kulik
N V
NV
Zobov
V V
VV
Giniyatullin
R K
RK
Mikhailov
A S
AS
Nikolaev
A E
AE
Akamsin
V D
VD
Reznik
V S
VS
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003621:Daphnia / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D007536:Isomerism; D047028:Macrocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D003904:Mitosporic Fungi / Q000187:drug effects; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014498:Uracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D047028:Macrocyclic Compounds; D014498:Uracil; D009584:Nitrogen