Relationship between the lipophilicity of gallic acid n-alquil esters' derivatives and both myeloperoxidase activity and HOCl scavenging.
The gallic acid and several n-alkyl gallates, with the same number of hydroxyl substituents, varying only in the side carbonic chain length, with respective lipophilicity defined through the C log P, were studied. It evidenced the structure-activity relationship of the myeloperoxidase activity inhibition and the hypochlorous acid scavenger property, as well as its low toxicity in rat hepatic tissue. The gallates with C log P below 3.0 (compounds 2-7) were more active against the enzyme activity, what means that the addition of 1-6 carbons (C log P between 0.92 and 2.92) at the side chain increased approximately 50% the gallic acid effect. However, a relationship between the HOCl scavenging capability and the lipophilicity was not observed. With these results it is possible to suggest that the gallates protect the HOCl targets through two mechanisms: inhibiting its production by the enzyme and scavenging the reactive specie.
Rosso
Rober
R
Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Santa Catarina, 88040-900, CP 476 Florianópolis, Brazil.
Vieira
Tiago O
TO
Leal
Paulo C
PC
Nunes
Ricardo J
RJ
Yunes
Rosendo A
RA
Creczynski-Pasa
Tânia B
TB
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002522:Chlorocebus aethiops; D004789:Enzyme Activation / Q000187:drug effects; D004952:Esters / Q000737:chemistry* / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000737:chemistry; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D057927:Hydrophobic and Hydrophilic Interactions; D006997:Hypochlorous Acid / Q000138:chemical synthesis* / Q000737:chemistry; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000737:chemistry / Q000201:enzymology; D008297:Male; D009195:Peroxidase / Q000037:antagonists & inhibitors / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D012984:Software; D012995:Solubility; D013329:Structure-Activity Relationship; D014709:Vero Cells
D004952:Esters; D016166:Free Radical Scavengers; D005707:Gallic Acid; D006997:Hypochlorous Acid; D009195:Peroxidase