Radical intensity and cytotoxicity of butylated hydroxyanisole and its orthobisphenol dimer.
The radical intensity of BHA (4-Hydroxy-3-t-butylanisole) and its dimer (3,3'-Di-t-butyl-5,5'-dimethoxy-1,1'-biphenyl-2,2'-diol, Bis-BHA) were compared with their cytotoxic activity. ESR spectroscopy showed that BHA produced characteristic five peaks of radicals under alkaline conditions (pH > 9.5). At higher pH, BHA radical rapidly disappeared, and progressively transformed into new radical species, as detected by the splitting of the ESR signal. BHA showed higher cytotoxic activity against salivary gland tumor cell line than against normal human gingival fibroblast. On the other hand, Bis-BHA did not produce any detectable amounts of radicals at wide ranges of pH, corresponding with its weaker cytotoxic activity as compared with BHA. BHA scavenged DPPH (1,1-Diphenyl-2-picrylhydrazyl) radical and superoxide anion, more efficiently than Bis-BHA. The present study demonstrated that BHA is more cytotoxic, produces higher amounts of radicals and more efficiently scavenges various radical species, as compared with Bis-BHA. This suggests the possible link between the cytotoxic activity and radical generation/scavenging activity in BHA-derived compounds.
Satoh
K
K
Analysis Center, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Atsumi
T
T
Sakagami
H
H
Kashiwagi
Y
Y
Ida
Y
Y
Ueha
T
T
Sugita
Y
Y
Yokoe
I
I
Fujisawa
S
S
D000975:Antioxidants / Q000737:chemistry*; D001241:Aspirin / Q000494:pharmacology; D015764:Bepridil / Q000031:analogs & derivatives / Q000494:pharmacology; D001713:Biphenyl Compounds; D002083:Butylated Hydroxyanisole / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D016166:Free Radical Scavengers / Q000737:chemistry*; D005609:Free Radicals / Q000737:chemistry; D005881:Gingiva / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008956:Models, Chemical; D010851:Picrates; D012468:Salivary Gland Neoplasms / Q000188:drug therapy; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D001713:Biphenyl Compounds; D016166:Free Radical Scavengers; D005609:Free Radicals; D010851:Picrates; D002083:Butylated Hydroxyanisole; D015764:Bepridil; C004931:1,1-diphenyl-2-picrylhydrazyl; D001241:Aspirin