Strong antioxidant activity of carane derivatives.
Oxidants play a significant role in causing oxidative stress, which underlies the pathogenesis of inflammation and rheumatoid arthritis. The processes associated with inflammatory responses are complex and often involve reactive oxygen species. There are many mediators that initiate and amplify the inflammatory response such as histamine, serotonin and metabolic products of arachidonic acid (thromboxane, prostaglandins and leukotrienes). In the present study, we examined the antioxidant activity of carane derivatives--KP-23 and its optical isomers--that possess strong local anesthetic and anti-inflammatory activity. The antioxidant effects (expressed as Trolox Equivalent Antioxidants Capacity, TEAC) were observed for one of the optical isomers of carane, a derivative of propranolol--KP-23R. The relative scavenging effect (%R) of ABTS+ by KP-23S, KP-23R and standards measured at 30 min was the following, listed in decreasing order: tetracaine > KP-23S > KP-23R > procaine > lignocaine > benzocaine (99, 85, 80, 38, 21 and 20%, respectively, at a concentration of 10 mM). The IC50 values also show strong antioxidant properties of the investigated KP compounds (ranging between 11-18 mM) and tetracaine (6.2 mM) compared to other local anesthetics (129-348 mM). Moreover, monoterpene derivatives were more effective as antioxidants than propranolol diastereoisomers (280-528 mM). We found that carane derivatives, in contrast to propranolol diastereoisomers, serve as potent antioxidants by scavenging radicals.
Librowski
Tadeusz
T
Department of Pharmacodynamics, Jagiellonian University, Medical College, Faculty of Pharmacy, Medyczna 9, PL 30-688 Kraków, Poland. mflibrow@kinga.cyf-kr.edu.pl
Moniczewski
Andrzej
A
D000319:Adrenergic beta-Antagonists / Q000737:chemistry; D000779:Anesthetics, Local / Q000737:chemistry; D000975:Antioxidants / Q000737:chemistry*; D052160:Benzothiazoles / Q000737:chemistry; D000081008:Bicyclic Monoterpenes; D002839:Chromans / Q000737:chemistry; D003514:Cyclohexylamines / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000737:chemistry; D007202:Indicators and Reagents; D011433:Propranolol / Q000737:chemistry; D013237:Stereoisomerism; D013451:Sulfonic Acids / Q000737:chemistry
D000319:Adrenergic beta-Antagonists; D000779:Anesthetics, Local; D000975:Antioxidants; D052160:Benzothiazoles; D000081008:Bicyclic Monoterpenes; D002839:Chromans; D003514:Cyclohexylamines; D016166:Free Radical Scavengers; D007202:Indicators and Reagents; D013451:Sulfonic Acids; C079300:4-(2-hydroxy-3-(N-isopropylamino)propoxyimino)carane; C002502:2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid; D011433:Propranolol; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid