Biological activity and physicochemical parameters of marine halogenated natural products 2,3,3',4,4',5,5'-heptachloro-1'-methyl-1,2'-bipyrrole and 2,4,6-tribromoanisole.
Physicochemical parameters (vapor pressure, water solubility, Henry's law constant) and biological activities of two halogenated natural products frequently detected in marine samples and food were determined. Synthetic 2,3,3',4,4',5,5'-heptachloro-1'-methyl-1,2'-bipyrrole (Q1) and 2,4,6-tribromoanisole (TBA) were available in pure form. The physicochemical parameters were in the range of anthropogenic chlorinated compounds of concern. The aqueous solubilities at 25 degrees C (S(w,25)) of Q1 and TBA were 4.6 microg/L and 12,200 microg/L, respectively, whereas subcooled liquid vapor pressures were 0.00168 Pa (Q1) and 0.06562 Pa (TBA) as measured by the gas chromatographic-retention time technique. Q1 was negative by established test systems for the determination of ethoxyresorufin-O-deethylase (EROD) induction and by sulforhodamine B assay. EROD induction potency was at least 10(-7) times lower than that of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). At a relatively high concentration (20 microM), Q1 inhibited specific binding of 2 nM [(3)H]TCDD to the in vitro-expressed human aryl hydrocarbon receptor (AHR) by 18%; lower concentrations showed no effect. Molecular modeling showed that Q1 is nonplanar, consistent with its relatively modest affinity as an AHR ligand. When tested for cell-growth inhibitory/cytocidal activity in human tumor cells, Q1 was only marginally, if at all, active with an IC(50) value >50 microM compared with five to ten times lower IC(50) values for potent cytotoxins tested in the test system used. Furthermore, standard pesticide tests on insecticidal, herbicidal, and fungicidal activity did not provide any significant activity at highest concentrations. For TBA, the results in all tests were comparable with Q1. The SRB assay was also applied to the halogenated natural product 4,6-dibromo-2-(2',4'-dibromo)phenoxyanisole, but no toxic response was found. Although it was apparent that Q1 and TBA had been proven to have relatively low biological activity in all tests performed, further research is necessary to clarify whether metabolites of the compounds eventually may possess a risk to humans or other living organisms. Nevertheless, the role of Q1 in nature remains uncertain.
Vetter
W
W
Institute of Food Chemistry, University of Hohenheim, Garbenstrasse 28, Stuttgart, D-70599, Germany. w-vetter@uni-hohenheim.de
Hahn
M E
ME
Tomy
G
G
Ruppe
S
S
Vatter
S
S
Chahbane
N
N
Lenoir
D
D
Schramm
K-W
KW
Scherer
G
G
D000818:Animals; D000840:Anisoles / Q000737:chemistry / Q000633:toxicity*; D001667:Binding, Competitive; D045744:Cell Line, Tumor; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000378:metabolism; D005456:Fluorescent Dyes; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000737:chemistry / Q000633:toxicity*; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism; D011758:Pyrroles / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000737:chemistry / Q000378:metabolism; D012235:Rhodamines / Q000378:metabolism
C503289:2,3,3',4,4',5,5'-heptachlor-1'-methyl-1,2'-bipyrrole; C471837:4,6-dibromo-2-(2',4'-dibromo)phenoxyanisole; D000840:Anisoles; D005456:Fluorescent Dyes; D006843:Hydrocarbons, Chlorinated; D000072317:Polychlorinated Dibenzodioxins; D011758:Pyrroles; D018336:Receptors, Aryl Hydrocarbon; D012235:Rhodamines; C022027:lissamine rhodamine B; C484217:2,4,6-tribromoanisole; D019363:Cytochrome P-450 CYP1A1