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Synthesis of 8-hydroxy-6-methoxy-3-pentyl-1H-isochromen-1-one from Tessmannia densiflora

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Aamer Saeed at Quaid-i-Azam University
Aamer Saeed
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Abstract

The synthesis of 8-hydroxy-6-methoxy-3-pentyl-1H-isochromen-1-one (1) isolated from the stem and root bark extracts of Tessmannia densiflora has been described. The reaction of 3,5-dimethoxyhomophthalic anhydride (2) with hexanoyl chloride in the presence of 1,1,3,3-tetramethylguanidine and triethylamine afforded 6,8-dimethoxy-3-pentylisocoumarin (3). Regioselective demethylation of the latter using anhydrous aluminum chloride furnished the title isocoumarin (1).
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EuropeanJournalofChemistry2(1)(2011)117‐119
EuropeanJournalofChemistry
ISSN2153‐2249(Print)/ISSN2153‐2257(Online)2011EURJCHEM
DOI:10.5155/eurjchem.2.1.117‐119.201
EuropeanJournalofChemistry
Journalhomepage:www.eurjchem.com
Synthesisof8‐hydroxy‐6‐methoxy‐3‐pentyl‐1H‐isochromen‐1‐one
fromTessmanniadensiflora
A
amerSaeed
D
epartmentofChemistry,Quaid‐I‐AzamUniversity,Islamabad,PK‐45320,Pakistan
Correspondingauthorat: DepartmentofChemistry,Quaid‐I‐AzamUniversity,Islamabad,PK‐45320,Pakistan.Tel.:+92.51.90642128;fax:+92.51.90642241.
E
‐mailaddress:aamersaeed@yahoo.com(A.Saeed).


COMMUNICATIONINFORMATION
A
BSTRACT
Received:08July2010
Receivedinrevisedform:05September2010
A
ccepted:18October2010
Online:31March2011
KEYWORDS
The synthesis of 8‐hydroxy‐6‐methoxy‐3‐pentyl‐1H‐isochromen‐1‐one (1) isolated from the
stemandrootbarkextractsofTessmanniadensiflorahasbeen described.Thereactionof3,5‐
dimethoxyhomophthalic anhydride (2) with hexanoyl chloride in the presence of 1,1,3,3‐
t
etramethylguanidine and triethylamine afforded 6,8‐dimethoxy‐3‐pentylisocoumarin (3).
Regioselectivedemethylationof the latter using anhydrous aluminum chloridefurnishedthe
t
itleisocoumarin(1).
Isocoumarin
Tessmanniadensiflora
3,5‐Dimethoxyhomophthalicacid
Antimalarial
3,5‐Dimethoxyhomophthalicanhydride
Mechanism
1.Introduction
Isocoumarins (1H‐2‐benzopyran‐1‐ones) are natural
lactonesthat areisolatedfrom awiderange ofnaturalsources
(microbes,plant,andinsects)andpossessanarrayofbiological
activities including nephratoxic, hepatotoxic, protease
inhibitory, antifungal, cytotoxic, immunomodulatory,
antiallergic, and antimalarial activities [1‐6]. Isocoumarins are
isomerictocoumarinswithaninvertedlactonering.Mostof
the natural isocoumarins posses a 3‐alkyl (C1‐C17) or a
substituted 3‐phenyl ring and 6,8‐dioxygenation due to their
typicalbiosyntheticorigin[7].
During investigations for botanical insecticides for the
controlofmalaria‐transmittingAnophelesgambiaemosquitoes,
Nkunyaandcoworkers[8]isolatedanumberofcompounds
fromthestemandrootbark extracts of Tessmanniadensiflora
Harms (family Caesalpiniaceae) that showed mosquito
larvicidalactivity.Theisolatedcompoundswereidentifiedas
nor‐halimanediterpenoidtessmannicacidanditsmethyl,2‐
methylisopropyland1‐methylbutylesters,5‐pentyl‐3‐methoxy‐
N‐butylaniline, and two unusualisocoumarins. The structures
ofthenewisocoumarinswereestablishedunambiguouslyas8‐
hydroxy‐6‐methoxy‐3‐pentyl‐1H‐isochromen‐1‐one (Figure 1)
and 7‐chloro‐8‐hydroxy‐6‐methoxy‐3‐pentylisocoumarin, res‐
pectively,byanalysisofspectroscopicdata[8].
Asacontinuanceofourfocusingonthesynthesis,
characterization, crystal structure,andbioevaluationofthis
importantclass of secondary metabolites[9‐14],asimpleand
efficient synthesis of the title compound was undertaken. The
structural simplicity, coupled with the bioactivity associated
withthismolecule, makes it an attractive target for synthesis.
Thesynthesisnotonlyconfirmsthe structural assignment but
also make it accessible for comprehensive evaluation of its
bioactivity.
Figure1.Isocoumarin(8‐hydrox
y
‐6‐methox
‐3‐pentyl‐1
H
‐isochromen‐1‐
one)fromTessmanniadensiflora.
2.Experimental
2.1.Instrumentation
Melting points were recorded using a digital Gallenkamp
(SANYO)modelMPDBM3.5apparatusandareuncorrected.1H
NMRand 13CNMRspectra were determinedinCDCl3solutions
at 300 MHz and 75 MHz respectively using a BrukerAM‐300
spectrophotometer.FT‐IRspectrawererecordedusinganFTS
3000MXspectrophotometer,Mass spectra(EI,70eV)onaGC‐
MSinstrument and elemental analyses with a LECO‐183 CHNS
analyzer.Allcompoundswerepurifiedbythicklayer
chromatographyusingsilicagelfromMerck(Darmstadt,
Germany).
2.2.Synthesis
2.2.1.6,8‐Dimethoxy‐3‐pentylisocoumarin(3)
Asolutionof3,5‐dimethoxyhomophthalicanhydride(2,1.0
g,4.50mmol)inacetonitrile(30mL)wasaddedslowlytoa
solutionof1,1,3,3‐tetramethylguanidine(TMG)(0.62mL,4.95
mmol) in acetonitrile (12 mL), while maintaining the internal
temperature ≤0 °C. Triethylamine (1.0 mL, 9.0 mmol) was
118 Saeed/EuropeanJournalofChemistry2(1)(2011)117‐119
addedinasingleportionfollowedbydropwiseadditionof
hexanoylchloride(1.23mL,7.20mmol).Thereactionmixture
wasfurtherstirredfor20minutes,allowedtowarmtoambient
temperatureandthenquenchedbyadditionof1MHCl(15
mL).Theorganiclayerwasseparated,washedwithsaturated
brinedriedandconcentrated.Thecrudecompoundwas
purified by thick layer chromatographyfollowed by
recrystallizationfrom methanoltoyieldisocoumarin3(0.42g,
1.53mmol,74%)(Scheme1).Asacolorlessoil;IR(KBr,ν,cm‐
1):2913,2849, 1722,1605,1575,1510,860,835,810.1H NMR
(CDCl3,,ppm):0.88(t,J=7.12Hz,3H,H‐5’),1.30(m,2H,H‐4’),
1.35 (quin, J=3.5 Hz,2H, H‐3’), 1.67 (quin, J=3.5 Hz, 2H, H‐2’),
2.47(2H,t,J=7.1Hz,H‐1’),3.85(s,3H,MeO),3.95 (s,3H,MeO),
6.09(s,1H,H4),6.39(d,J=2.2Hz,1H,H‐7),6.47(d,J=2.1Hz,
1H, H‐5). 13C NMR (CDCl3, , ppm): 168.1 (C=O), 167.3 (C6),
163.7 (C8), 159.6 (C3), 141.8 (C9), 103.4 (C4), 102.2 ( C5),
100.9 ( C7), 99.9 ( C10), 55.3 (MeO), 56.6 (MeO), 33.3 (C1'),
31.1(C3'),26.4(C2'),22.3(C4'),14.1(C5').MS(m/z):276(16),
219 (18), 206 (52), 191 (15), 177 (27), 165 (14), 164 (98).
Anal.Calcd. for C16H20O4: C, 69.54; H, 7.30. Found: C, 69.71; H,
7.15.
Scheme1
2.2.2.6‐Methoxy‐8‐hydroxy‐3‐pentylisocoumarin(1)
Aluminumchloride(0.83g,6.24mmol)wasaddedtoa
stirredsolutionof3(0.35g, 1.26mmol)infreshlydistilleddry
nitrobenzene(10mL).Thereactionmixturewasstirredat50‐
60°Cfor6h,thenpouredintoicewaterandacidifiedwith0.5
NHCl.Theacidicsolutionwasextractedwithdiethylether
(3x50 mL) and stirred for 10 min. The layers wereseparated
and the aqueous layer extracted with dichloromethane (2x50
mL)andthenthecombinedorganicextractswashedwith2.5M
NaOH(2x60mL).Thebasicsolutionwasextractedwithdiethyl
ether,acidifiedandagainextractedwithdiethylether.Thelast
extractwasevaporatedandresiduepurifiedbythicklayer
chromatography(petroleumether:ethylacetate(8:2))toafford
(1)(0.20g, 0.8mmol, 62%). M.p.:76‐78 °C(Lit.[8]:79‐80°C).
1HNMR(CDCl3,,ppm):0.89(t, J=7.12 Hz, 3H, H‐5’), 1.31 (m,
2H, H‐4’), 1.39 (quin,J=3.5 Hz, 2H, H‐3’), 1.68 (quin, J=3.5 Hz,
2H,H‐2’),2.49(t,J=7.61Hz,3H,H‐1’),3.85(s,3H,MeO),6.18(s,
1H,H4),6.39(d,J=2.2Hz,1H,H7),6.47(d,J=2.2Hz,1H,H5),
11.2(1H,brs,OH).13CNMR(CDCl3,,ppm):164.4(C=O),163.7
(C8),163.3(C6),159.7(C3),142.4(C9),103.1(C4),102.9(C5),
100.3(C7), 98.7 (C10), 56.3 (MeO), 33.3(C1'),31.1(C3'),26.4
(C2'),22.3 (C4'),13.9(C5'). MS(m/z):262 (37),206(52), 191
(15),177(27),164(100),149(29).Anal.Calcd.forC15H18O4:C,
68.68;H,6.92;foundC,68.12;H,7.01.
3.Resultsanddiscussion
3,5‐Dimethoxyhomophthalic acid [15] was efficiently
convertedinto corresponding anhydride (2)byrefluxingwith
aceticanhydrideindrytoluene.Theanhydride2inacetonitrile
wasaddedtoasolutionof1,1,3,3‐tetramethylguanidine(TMG)
inthesamesolventat0°Cfollowedbyadditionof
triethylamine [16].Treatmentofthereactionmixturewith
hexanoyl chloride furnished the 6,8‐dimethoxy‐3‐pentyl‐
isocoumarin(3) in 74% yield. Isocoumarin 3 exhibited the
characteristicsingletforH‐4olefinicprotonat6.09ppm,the
tripletforH‐1’at2.46ppm(J=7.1Hz)andthecarbonsignalsat
103.5 (C‐4) and 159.3 (C‐3) and 168.1 (C=O) ppm. The δ‐
lactoniccarbonylstretchingintheIRspectrumappearedat
1725 cm‐1. The construction of isocoumarin 3fromthe
anhydride2may bevisualizedby the lossofabenzylic proton
tobasetoaffordtheresonancestabilizedanionicspecies(2a
and2b),whichattacksthehexanoylchloridetogivethe4‐
hexanoyl‐6,8‐dimethoxyisochroman‐1,3‐dione intermediate I.
LossofprotontothebaseaffordsthespeciesIIa,b,whichupon
intramolecular O‐acylationfurnishesthetricyclicintermediate
III,which under basic influence undergoes ring opening to
affordIV.Decarboxylationfollowedbyisomerizationofthe
latterprovidedtheisocoumarin3(Scheme2).
Scheme2

The C‐8 methoxyl in 6,8‐dimethoxy‐3‐methylisocoumarin
(3) was regioselectively demethylated using anhydrous
aluminum chloride in dry nitrobenzene [17‐18],dueto
hydrogenbondingoftheresultinghydroxylwiththeperiplanar
lactoniccarbonyltoyieldthe8‐hydroxy‐6‐methoxy‐3‐
pentylisocoumarin(1).Inadditiontothedisappearanceofthe
C‐8methoxygroupat3.95ppm,thedownfieldshiftofsinglet
forH‐4andthetripletforH‐1’to6.15and2.48ppm(J=7.6Hz),
respectively, was detected. A similar shift for C‐4 and C‐3
(104.0 and 156.2 ppm, respectively) was also noted. The
lactoniccarbonylabsorptionwasalsoloweredto1685cm‐1due
tochelationwithC‐8hydroxylwhichappearedat11.2ppm.
4.Conclusion
Anefficientsynthesisofanaturalisocoumarinhasbeen
achieved.Alikelypathwayforformationofisocoumarin3from
anhydride2hasalsobeenproposed.
Acknowledgement
Theauthor gratefully acknowledges a research grant from
theHigherEducationCommissionofPakistanunderprojectNo.
20‐Miscel/R&D/00/3834.
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Supplementary resource (1)

EJC C-5 iso-11
Data
July 2013
Aamer Saeed
... The most common drug prescribed for malaria patients is chloroquine, but some derivatives of 3,4-dihydroisocoumarin, mullein 37a-37d, produced by Botryosphaeria rhodina, an endophytic fungus, show effective antimalarial activity (Figure 9). 47 Some isocoumarin derivatives, 8-hydroxy-6-methoxy-3-pentyl-1H-isochromen-1-one 38a-38b 48,49 and halorosellins 39, 50 isolated from the bark and stem of Tessmannia densiflora and Halorosellinia oceanica, respectively, also showed antimalarial activity ( Figure 9 Ceratocystis fimbriata, a fungus, is a source of isocoumarins 40a-40d that are known for their phytotoxic activity on leaves of coffee trees, and also they are responsible for fruit withering with trunk canker in adult coffee trees ( Figure 10). 51 Other derivatives of 3,4-dihydroisocoumarin 41a-41b extracted from the fungus Ceratocystis ulmi inhibit the growth of rice seedlings and lesions on the leaves of pear trees ( Figure 10). ...
Isocoumarins and 3,4-dihydroisocoumarins, amazing natural products: A review
Article
Full-text available
  • Jan 2017
  • TURK J CHEM
The isocoumarins are naturally occurring lactones that constitute an important class of natural products exhibiting an array of biological activities. A wide variety of these lactones have been isolated from natural sources and, due to their remarkable bioactivities and structural diversity, great attention has been focused on their synthesis. This review article focuses on their structural diversity, biological applications, and commonly used synthetic modes.
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Intramolecular transesterification of depsides yields fluorescent 1H-isochromen-1-ones: Application as a chemical probe for lichen determination
Article
  • Mar 2022
  • PHYTOCHEMISTRY
The reactivity of eight purified depsides obtained from six european lichens and that display as 2-oxoalkyl chain in ortho-position of the ester bond was explored. These depsides were found to lead to 1H-Isochromen-1-ones, which exhibit a distinctive blue fluorescence at 365 nm, in the presence of a 10% aqueous solution of KOH. A mechanistic explanation, involving the formation of an enolate intermediate and intramolecular transesterification, was proposed and validated by DFT. By exploiting this fluorescent phenomenon, we conceived a chemical probe (the KUV probe) that is useful for lichen determination, as exemplified on a selection of European Porpidia species.
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Synthesis of Isocoumarin Compounds, 8-Hydroxy-6-methoxy-3-Pentyl-1H-Isochromen-1-one and Fusariumin Analog Using Palladium-Catalyzed Carbonylation Trapping with O-Enolate
Article
  • Jan 2017
  • HETEROCYCLES
Concise synthesis of 6,8-dialkoxyisocoumarin framework was achieved using Pd-catalyzed carbonylation trapping with O-enolate. This methodology was applied to the synthesis of 8-hydroxy-6-methoxy-3-pentyl-1H-isochromen-1-one isolated from Tessmannia densiflora and fusariumin analog.
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Synthesis of (±)-kigelin
Article
Full-text available
  • Jul 2005
  • J BRAZIL CHEM SOC
A simple synthesis of racemic 8-hydroxy-6,7-dimethoxy-3-methyl-3,4-dihydroisocoumarin or kigelin, a metabolite of Aspergillus terreus and Kigelia pinnata, exhibiting several bioactivities, is described. 3,4,5-Trimethoxyhomophthalic acid was refluxed with acetic anhydride in dry pyridine to afford 2,3,4-trimethoxy-6-(2-oxopropyl)benzoic acid. Reduction of the latter followed by cyclodehydration yielded 6,7,8-trimethoxy-3-methyl-3,4-dihydroisocoumarin which on regioselective demethylation furnished the (±)-kigelin.
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Stereoselective Synthesis of (3R)‐3,4‐Dihydro‐6,8‐dimethoxy‐3‐undecyl‐ 1H‐[2]benzopyran‐1‐one and Derivatives, Metabolites from Ononis natrix
Article
Full-text available
  • Feb 2003
  • HELV CHIM ACTA
A short stereoselective synthesis of (3R)-3,4-dihydro-6,8-dimethoxy-3-undecyl-1H-[2]benzopyran-1-one and derivatives isolated from Ononis natrix has been described. Condensation of dodecanoyl chloride with 3,5-dimethoxyhomophthalic acid afforded 6,8-dimethoxy-3-undecylisocoumarin 3, which, on sequential saponification and esterification, yielded the keto ester 5. Enantioselective reduction of 5 with TarB-NO2/LiBH4 directly furnished the title dihydroisocoumarin 1a in 80% ee (82% yield). Partial as well as complete demethylation of the latter provided the dihydroisocoumarins 1b and 1c, respectively. Diastereotopy of the CH2 H-atoms on either side of the stereogenic center (C(3)) and the mass-fragmentation pattern of the dihydroisocoumarins have also been described. All of the compounds synthesized were examined in vitro for antifungal activity.
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Synthesis of 6,8-Dihydroxy-3-(2′-Acetyl-3′, 5′-Dihydroxyphenyl)Methylisocoumarin Related to Feralolide
Article
Full-text available
  • Sep 2004
Base-catalyzed self-condensation of 3,5-dimethoxyhomophthalic acid (2) directly furnished the 6,8-dimethoxy-3-(2'-carboxy-3',5'-dimethoxyphenyl)methylisocoumarin (3) which on successive treatment with oxalyl chloride, diazomethane and hydrolysis afforded the corresponding 2'-acetylisocoumarin (5). Complete demethylation of the latter yielded the 6,8-dihydroxy-3-(2'-acetyl-3',5'-dihydroxyphenyl)methylisocoumarin (6) related to the natural product feralolide (1a).
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Synthesis of chlorinated isocoumarin derivatives
Article
  • Jan 1982
  • Perkin Trans 1
Syntheses of 5-chloro-, 7-chloro-, and 5,7-dichloro-Isocoumarin derivatives, including the fungal metabolites 5-chloro-3,4-dihydro-8-hydroxy-6-methoxy-3-methylisocoumarin (3), 7-chloro-3,4-dihydro-8-hydroxy-6-methoxy-3-methylisocoumarin (2), and 5,7-dichloro-3,4-dihydro-8-hydroxy-6-methoxy-3-methylisocoumarin (1), are described. This is the first total synthesis of compounds (1) and (2) to be reported. The synthetic route involves carboxylation of chlorinated 2,4-dimethoxy-6-methylbenzoic acids, yielding homophthalic acids. The corresponding homophthalic anhydrides were acetylated and decarboxylated to produce isocoumarins. The naturally occurring 7-chloro-8-hydroxy-6-methoxy-3-methylisocoumarin (7) has been synthesised for the first time.
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Microwave‐Assisted Synthesis of cAMP Phosphodiesterase Inhibitor 8‐Hydroxy‐6,7‐dimethoxy‐3‐hydroxymethylisocoumarin
Article
  • May 2007
  • SYNTHETIC COMMUN
An efficient microwave‐assisted synthesis of 8‐hydroxy‐6,7‐dimethoxy‐3‐hydroxymethyl isocoumarin (1), a metabolite of Streptomyces mobaraensis and structural relative of reticulol and cytogenin that possesses potent cyclic nucleotide phosphodiesterase inhibitor activity, is described. 3,4,5‐Trimethoxyhomophthalic acid (2) was condensed with acetoxyacetyl chloride under microwave irradiation and the acid hydrolysis of resulting 6,7,8‐trimethoxy‐3‐acetoxymethylisocoumarin (3) afforded the 6,7,8‐trimethoxy‐3‐hydroxymethylisocoumarin (4). Regioselective demethylation of the latter using magnesium iodide in THF yielded the title compound (1).
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Synthesis of (±)-6-O-methyl and 7-demethylannulatomarin
Article
  • Jan 2010
  • J ASIAN NAT PROD RES
Synthesis of 6-O-methyl and 7-demethyl derivatives of annulatomarin (1) (6,8-dihydroxy-7-methoxy-3-phenyl-3,4-dihydroisocoumarin) isolated from the aerial parts of Hypericum annulatum is described. The key step involves an efficient, microwave-accelerated solvent and catalyst-free condensation of methyl benzoate with 3,4,5-trimethoxyhomophthalic acid (2) to afford 6,7,8-trimethoxy-3-phenylisocoumarin (3). Saponification of the latter to keto acid (4) followed reduction to furnish 6,7,8-trimethoxy-3-phenyl-3,4-dihydroisocoumarin (5), which was either regioselectively demethylated to ( +/- )-6-O-methylannulatomarin (6) or completely demethylated to ( +/- )-7-demethylannulatomarin (7).
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Anti-mosquito and antimicrobial nor-halimanoids, isocoumarins and an anilinoid from Tessmannia densiflora
Article
  • Sep 2009
The nor-halimane diterpenoid tessmannic acid and its methyl, 2-methylisopropyl and 1-methylbutyl esters, the unusual isocoumarins 8-hydroxy-6-methoxy-3-pentylisocoumarin and 7-chloro-8-hydroxy-6-methoxy-3-pentylisocoumarin, and 5-pentyl-3-methoxy-N-butylaniline were isolated from the stem and root bark extracts of Tessmannia densiflora Harms (Caesalpiniaceae) that showed mosquito larvicidal activity. The structures were determined on interpretation of spectroscopic data. Tessmannic acid and its methyl ester exhibited antibacterial and antifungal activity. The compounds also caused high larvae and adult Anopheles gambiae mosquitoe mortality effects, and stronger mosquito repellency than that shown by the standard repellent DEET, hence indicating Tessmannia species to be potential sources of bioactive natural products.
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Metabolites from Fungi 15. New Isocoumarins from an Endophytic Fungus Isolated from the Canadian Thistle Cirsium arvense
Article
  • Feb 2001
  • Nat Prod Lett
One known (1) and five new polyketide metabolites (2-6) were isolated from the culture extract of an endophytic fungus, Mycelia sterila, from the Canadian thistle Cirsium arvense. Compounds 1-4 are members of the isocoumarin family, whereas metabolite 5 is a dihydrobenzofuran and 6 has an open chain structure. All compounds have an unusual methyl group at the aromatic ring that does not fit into the usual polyketide pattern.
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Formal Synthesis of Angiogenesis Inhibitor NM-3
Article
  • Aug 2003
We report the formal synthesis of angiogenesis inhibitor NM-3 (1) in six steps from either of the 2,4-dimethoxyhalobenzenes 13a,b or 3,5-dimethoxychlorobenzene (13c). The first key reaction is the regiospecific alkylation/rearrangement between the aryne derived from 13a-c with sodium diethylmalonate in THF to produce diester 11, which after hydrolysis and cyclization affords homophthalic anhydride 3. The second is the reaction of anhydride 3 with either ethyl 2-methylmalonate (28a), in the presence of 1,1'-carbonyldiimidazole, or ethyl-2-methylmalonyl chloride (28b) under basic conditions to afford key isocoumarin 27. The conversion of 27 constitutes a formal synthesis of NM-3.
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Intestinal Anti-Inflammatory Activity of Paepalantine, an Isocoumarin Isolated from the Capitula of Paepalanthus bromelioides, in the Trinitrobenzenesulphonic Acid Model of Rat Colitis
Article
  • May 2004
The preventative intestinal anti-inflammatory activity of paepalantine, an isocoumarin isolated from the capitula of Paepalanthus bromelioides, was tested in the trinitrobenzenesulphonic acid (TNBS) model of rat colitis. This was performed in two different experimental settings, i. e. when the colonic mucosa is intact or when the mucosa is in process of recovery after an initial insult. The results obtained revealed that the paepalantine pretreatment, at doses of 5 and 10 mg/kg, significantly attenuated the colonic damage induced by TNBS in both situations, as it was evidenced both histologically and biochemically. This beneficial effect was associated with an improvement in the colonic oxidative status, since paepalantine prevented the glutathione depletion that occurred as a consequence of the colonic inflammation. In addition, the intestinal anti-inflammatory effect exerted by this isocoumarin was associated with an inhibition of colonic nitric oxide activity, which is upregulated as a consequence of the inflammatory process. In conclusion, the preventative effect exerted by paepalantine in the TNBS model of rat colitis is probably related with its antioxidant properties. Abbreviations AP:Alkaline phosphatase IBD:Inflammatory bowel disease GSH:Glutathione MPO:Myeloperoxidase NOS:Nitric oxide synthase TNBS:Trinitrobenzenesulphonic acid
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