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Synthesis and pharmacological investigation of novel 3-(benzyl)-2-substituted amino-3H-quinazolin-4-ones as analgesic and anti-inflammatory agents
Abstract
A variety of novel 3-(benzyl)-2-substituted amino-quinazolin-4(3H)-ones were synthesized by reacting the amino group of 3-benzyl-2-hydrazino quinazolin-4(3H)-one with a variety of aldehydes and ketones. The starting material, 3-benzyl-2-hydrazino quinazolin-4(3H)-one, was synthesized from benzyl amine. The title compounds were investigated for analgesic, anti-inflammatory, and ulcerogenic
index activities. The compound 3-benzyl-2-[N’-(1-ethyl-propylidene)-hydrazino]-3H-quinazolin-4-one (AS2) emerged as the most active compound of the series and is moderately more potent in its analgesic and anti-inflammatory activities
when compared to the reference standard diclofenac sodium. Interestingly the test compounds showed only mild ulcerogenic potential
when compared to aspirin.
... Quinazolinone nucleus has been getting distinction due to the fact that its derivatives have been found to own wide spectrum of pharmacological properties. Quinazolin-4(3H)-one outgrowth are advantageous heterocycles, possessing potent pharmacognosy activities such as antibacterial, antifungal, analgesic, anti-inflammatory, anthelminthic, anticancer, anticonvulsant, antihistaminic, anti-HIV, antiproliferative, antitubercular, antiviral, CNS depressant, cytotoxicity, diuretic and hypolipidemic [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]. ...
... The versatility in pharmacological activities and stability of the quinazoline nucleus has inspired medicinal chemists to introduce many bioactive moieties to this nucleus to synthesize new potential medicinal agents. Quinazoline and quinazolinone derivatives have continuing to attract a widespread interest for an extended time because of their various pharmacological activities like antibacterial [4,5], antitubercular [6], antifungal [7], hypoglycemic [8] and anti tumour [9]. During a literature survey for our ongoing medicinal chemistry research program, we found that quinazolines and condensed quinazolines exhibit potent central nervous systems (CNS) activities like analgesic, antiinflammatory [12] and anticonvulsant [13]. ...
... [6] Among various ligands quinazolinone containing nitrogen, sulphur donor atoms have received much attention in recent years. These compounds exhibit varieties of biological properties, especially anti-inflammatory, [7] anticonvulsant, [8] antihyperten- sive, [9] anticancer, [10,11] antimalarial, [12] antibacterial, [13] etc. The presence of endocyclic hard N-donor and exocyclic soft S-donor atoms in the backbone of these ligands enable them to react readily with transition metal ions to form stable complexes with unusual structural and chemical properties. ...
Several complexes of the type [M(L)(en or phen)(H2O)X] (1a-4a and 1b-4b); where M = Co(II) and Cu(II); L = 2-mercapto-3-phenyl-quinazolin-4(3H)-one; en = ethylenediamine, phen = 1,10-phenanthroline; X = N− 3 and NCS− have been prepared and characterized. The complex formation occurred through both nitrogen and sulphur atom of the ligand L. Electronic spectra and magnetic moment values suggest octahedral geometry for all complexes. The thermal behavior of the complexes revealed that the phen complexes are thermally more stable than the en complexes. The electrochemical behavior of the Cu(II) complexes showed that phen complexes appeared at more positive potential than corresponding en complexes.
... 2010; 78: 171–193. antihistaminic, anti-HIV, antiproliferative, antitubercular, antiviral, CNS depressant, cytotoxicity, diuretic and hypolipidemic15161718192021222324252627282930. 1,3,4-Qxadiazoles and quinazolin-4(3H)-ones having various heterocycles possess wide range of pharmacological properties. ...
In attempt to find new pharmacologically active molecules, we report here the synthesis and in vitro antimicrobial activity of various 3-(1,3,4-oxadiazol-2-yl)-quinazolin-4(3H)-ones. The antimicrobial activity of title compounds were examined against two gram positive bacteria (S. aureus, S. pyogenes), two gram negative bacteria (E. coli, P. aeruginosa) and three fungi (C. albicans, A. niger, A. clavatus) using the broth microdilution method. Some derivatives bearing a bromo or iodo group exhibited very good antimicrobial activity.
Many quinazoline derivatives have been synthesized over the last few decades with great pharmacological potential, such as antimalarial, anti-inflammatory, antimicrobial, anticancer, and antiviral. But so far, no quinazoline–artemisinin hybrids have been reported in the literature. In the present study, five novel quinazoline–artemisinin hybrids were synthesized and evaluated for their in vitro biological activity against malarial parasites (Plasmodium falciparum 3D7), leukemia cells (CCRF-CEM and CEM/ADR5000), and human cytomegalovirus. Remarkably, hybrid 9 (EC50 = 1.4 nM), the most active antimalarial compound of this study, was not only more potent than artesunic acid (EC50 = 9.7 nM) but at the same time more active than the clinically used drugs dihydroartemisinin (EC50 = 2.4 nM) and chloroquine (EC50 = 9.8 nM). Furthermore, hybrids 9 and 10 were the most potent compounds with regard to anticytomegaloviral activity (EC50 = 0.15–0.21 μM). They were able to outperform ganciclovir (EC50 = 2.6 μM), which is the relevant standard drug of antiviral therapy, by a factor of 12–17. Moreover, we identified a new highly active quinazoline derivative, compound 14, that is most effective in suppressing cytomegalovirus replication with an EC50 value in the nanomolar range (EC50 = 50 nM). In addition, hybrid 9 exhibited an antileukemia effect similar to that of artesunic acid, with EC50 values in the low micromolar range, and was 45 times more active toward the multidrug-resistant CEM/ADR5000 cells (EC50 = 0.5 μM) than the standard drug doxorubicin.
A series of novel 2-thioxo quinazolinonyl chalcones were synthesized by the Claisen-Schmidt condensation reaction of 1-acetyl-2-thioxo quinazolin-4-(3H)-ones with benzaldehyde. The synthesized compounds were characterized by physical, elemental, IR, 1H NMR and mass spectral data. Further, they were screened for in vivo analgesic and anti-inflammatory activities. Among them, the title compounds 3e, 3f, 3g, 3k, 3l, 3q and 3r exhibited promising analgesic and anti inflammatory activities.
This article outlines the medicinal and biological significance of one of the most important heterocycles, the quinazoline. Quinazoline is a highly active scaffold exhibiting wide variety of medicinal and biological activities. An attempt is made in this article to cover the medicinally active compounds, along with the recent discoveries, which were reported to posses various biological activities. This is might be helpful in the development of these novel lead molecules to potential drug candidates.
A new approach to synthesize quinazoline-4(3H)-ones was achieved by oxidation of quinazolines using peracetic acid, which possesses some advantages of economic reagents, simplified operation, high efficiency, and environmental friendliness. Application of this method allowed us to synthesize a series of quinazolin-4(3H)-ones with different substituents at 6 and 7 positions in good to excellent yields, including the key intermediates of tyrosine kinase inhibitors such as PD153035, Erlotinib, and Gefitinib.[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]
Some copper(I) complexes of the formula [Cu(L)(PPh3)2]X (1–4) [where L = 2-phenyl-3-(benzylamino)-
1,2-dihydroquinazolin-4(3H)-one; PPh3 = triphenylphosphine; X = Cl�, NO3
�, ClO4
� and BF4
�] have been
prepared and characterized on the basis of elemental analysis, IR, UV–Vis and 1H NMR spectral studies.
The representative complex of the series 4 has been characterized by single crystal X-ray diffraction
which reveal that in the complex the central copper(I) ion assumes the irregular distorted-tetrahedral
geometry. Cyclic voltammetry of the complexes indicate a quasireversible redox behavior corresponding
to Cu(II)/Cu(I) couple. All the complexes exhibit intraligand (p?p⁄) fluorescence with high quantum
yield in dichloromethane solution.
Some mixed ligand complexes of the type [M(L)(en or phen)(X)2]; where M=Mn(II), Co(II) or Ni(II); L=2-phenyl-3-(benzylamino)-1,2-dihydroquinazolin-4(3H)-one; en=ethylenediamine, phen=1,10-phenanthroline; X=N3
− or NCS− have been prepared. All the complexes were characterized by physico-chemical, spectroscopic and thermal studies. On the basis
of electronic spectra and magnetic susceptibility measurements, an octahedral geometry has been proposed for all the complexes.
The phen complexes are thermally more stable than the en complexes. The electrochemical behavior of the Ni(II) complexes showed that the complexes of phen are reduced at more positive potential compared to the corresponding en complexes.
Twelve as yet, unreported complexes of luteolin were synthesized with various rare earth ions through refluxing in ethanol.
The characterization of these complexes by elemental analysis, infrared spectra, and differential scanning calorimeter demonstrated
that luteolin coordinated the various rare earth ions in a similar manner. Experiments designed to study the anti-inflammatory
activities of these rare earth-luteolin complexes indicated that they had a significant inhibitory effect on xylene-induced
ear edema in mice. Five complexes containing La3+, Ho3+, Yb3+, Lu3+, and Y3+ were equally effective as luteolin and dexamethasone (DXM). However, their inhibitory effects on carrageenan-induced paw
edema in mice, although significant, were weaker than that of either luteolin alone or DXM.
KeywordsLuteolin–Rare earth metal–Complex–Anti-inflammatory activity
Some mixed ligand Cu(II) complexes of the type [Cu(L)(en)X(2)] (1a-3a), [Cu(L)(en)](ClO(4))(2) (4a), [Cu(L)(phen)X(2)] (1b-3b) and [Cu(L)(phen)](ClO(4))(2) (4b) [where L = 2-phenyl-3-(benzylamino)-1,2-dihydroquinazoline-4-(3H)-one; en = ethylenediamine; phen = 1,10-phenanthroline; X = Cl(-), N(3)(-) and NCS(-)] have been prepared. The complexes were characterized on the basis of elemental analysis, molar conductance, magnetic moment, IR, UV-vis, mass, ESR and thermal studies. On the basis of electronic spectral data and magnetic susceptibility measurement octahedral geometry has been proposed for 1a-3a and 1b-3b and square-planer geometry for 4a and 4b. The ESR spectral data of complexes provided information about their structure on the basis of Hamiltonian parameters and degree of covalency. The electrochemical behaviour of mixed ligand Cu(II) complexes was studied which showed that complexes of phen appear at more positive potential as compared to those for corresponding en complexes.
A number of 3-substituted-2-(substituted-phenoxymethyl) quinazolin-4(3H)-one derivatives 4a,b, 5a-c, 6, 7a-f, 8a-e and 9a,b have been synthesized. Their structures have been elucidated on the basis of elemental analyses and spectroscopic studies (IR, 1H-NMR, MS). A preliminary evaluation of the anticonvulsant activity of the prepared compounds has indicated that compounds 4b, 7b-f, 8a and 9b exhibit significant anticonvulsant activity, while compounds 6, 8b and 8d show mild to moderate activity.
A variety of novel 3-(3-methylphenyl)-2-substituted amino-3H-quinazolin-4-ones were synthesized by reacting the amino group of 2-hydrazino-3-(3-methylphenyl)-3H-quinazolin-4-one with a variety of aldehydes and ketones. The starting material 2-hydrazino-3-(3-methylphenyl)-3H-quinazolin-4-one was synthesized from 3-methyl aniline. The title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic index activities. Compound 2-(1-ethylpropylidene-hydrazino)-3-(3-methylphenyl)-3H-quinazolin-4-one (AS2) was the most active analgesic agent. Compound 2-(1-methylbutylidene-hydrazino)-3-(3-methylphenyl)-3H-quinazolin-4-one (AS3) was the most active anti-inflammatory agent and was moderately more potent than the reference standard diclofenac sodium. The test compounds showed only mild ulcerogenic potential compared with aspirin.
A new series of 3-(4-ethylphenyl)-2-substituted amino-3H-quinazolin-4-ones were synthesized by reacting the amino group of 2-hydrazino-3-(4-ethylphenyl)-3H-quinazolin-4-one from 4-ethyl aniline with a variety of aldehydes and ketones. The title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic index activities. The compound 2-(N'-3-pentylidene-hydrazino)-3-(4-ethylphenyl)-3H-quinazolin-4-one (AS2) emerged as the most active compound of the series and was moderately more potent than the reference standard diclofenac sodium. Interestingly the test compounds showed only mild ulcerogenic potential when compared to aspirin.
A series of novel 2-phenyl-3-substituted quinazolin-4(3H)-ones have been synthesized by treating methyl-N-(2-phenyl quinazolin-3-yl-4(3H)-one) dithiocarbamate with different amines, the starting material dithiocarbamate was synthesized from anthranilic acid. The title compounds were investigated for analgesic, anti-inflammatory and antibacterial activities. All the test compounds exhibited significant activity, the compounds A1, A2 and A3 shown more potent analgesic activity, and the compound A3 shown more potent anti-inflammatory activity than the reference standard diclofenac sodium.
A series of 2-Substituted (1,3,4) thiadiazolo quinazolines were synthesized by the cyclocondensation of 3-amino-2-mercapto quinazolin-4(3H)-ones with various one-carbon donors and screened for their CNS activities (analgesic, anti-inflammatory, sedative-hypnotic and anticonvulsant). Compound III showed good CNS depressant activity, and it is comparable with the reference standard diazepam. While all the test compounds offered significant protection against strychnine-induced and hypoxic induced convulsion, compound III exhibited equivalent activity with the standard diazepam at the dose tested, and it was found to be significant when compared to control.
A series of novel 2-phenyl-3-substituted quinazolin-4(3H)-ones have been synthesized by treating methyl-N-(2-phenyl quinazolin-3-yl-4(3H)-one) dithiocarbamate with different amines, the starting material dithiocarbamate was synthesized from anthranilic acid. The title compounds were investigated for analgesic, anti-inflammatory and antibacterial activities. All the test compounds exhibited significant activity, the compounds A1, A2 and A3 shown more potent analgesic activity, and the compound A3 shown more potent anti-inflammatory activity than the reference standard diclofenac sodium.
A series of novel 2-methyl-3-substituted quinazolin-4-(3H)-ones have been synthesized by treating (2-methyl-4-oxo-3H-quinazolin-3-yl)dithiocarbamic acid methyl ester with different amines, the starting material dithiocarbamate was synthesized from anthranilic acid. The compounds synthesized were investigated for analgesic, anti-inflammatory and antibacterial activities. All the test compounds exhibited significant activity, the compounds VA2, VA3 and VA4 shown more potent analgesic activity, and the compounds VA3 and VA4 shown more potent anti-inflammatory activity than the reference compound diclofinac sodium.
Two series of N -[5-(2-furanyl)-2-methyl-4-oxo-4 H -thieno[2,3- d ]pyrimidin-3-yl]-carboxamide ( 4a – m ) and 3-substituted-5-(2-furanyl)-2-methyl-3 H -thieno[2,3- d ]pyrimidin-4-ones ( 5a – m ) were synthesised using appropriate synthetic route. All the test compounds 4a – m and 5a – m were assayed in vitro for antibacterial activity against two different strains of Gram-negative ( Escherichia coli and S. typhi ) and Gram-positive ( S. aureus , B. subtilis ) bacteria and the antimycobacterial activity was evaluated against M. tuberculosis and M. avium strains. The minimum inhibitory concentration (MIC) was determined for test compounds as well as for reference standards. The test compounds have shown significant antibacterial and antimycobacterial activity against all the microbial strains used, when tested in vitro. In general, along with the thienopyrimidinone ring, substituted amido or imino side chain at position 3 is essential for antimicrobial activity. Among the compounds tested, compounds 4c , 4e and 4g in N -[5-(2-furanyl)-2-methyl-4-oxo-4 H -thieno[2,3- d ]pyrimidin-3-yl]-carboxamide series and compounds 5c , 5e and 5g in 3-substituted-5-(2-furanyl)-2-methyl-3 H -thieno[2,3- d ]pyrimidin-4-ones series were found to be the most potent. Further the toxicity of most potent compounds 4c , 4e and 4g and 5c , 5e and 5g were assessed using hemolytic assay and minimal hemolytic concentration (MHCs) were determined. In general, test compounds were found to be non-toxic up to a dose level of 200 μmol L −1 (MHC).
The multitalented therapeutic agent that is used to relieve a variety of ailments, acetylsalicylic acid (Aspirin®) is facing new competition. The goal is to use tailor-made inhibitors of cyclooxygenase-2 to selectively reduce pain while minimizing side effects. Do these new drugs represent a new generation of nonsteroidal pain relievers?
To assess the specific role played by adrenals in the production of restraint ulcers in the stomach of albino rats, bilaterally adrenalectomized rats were exposed to stress by a restraint technique and the gastric ulcers that developed were compared with those of adrenal-intact rats under similar conditions.The results show that in vagus-intact, bilaterally adrenalectomized rats, the ulcer index comes down to 0.016 from 0.11 in vagus-intact, adrenal-intact rats. This clearly demonstrates that adrenals play a significant role in the production of restraint ulcers in the gastric mucosa of the albino rats.
Experiments with guinea-pig lung suggest that some of the therapeutic effects of sodium salicylate and aspirin-like drugs are due to inhibition of the synthesis of prostaglandins.
Acute environmental heat (40±2°C) and other physiological stressful situations increased the pain threshold to radiant heat in rats and mice. Naloxone pretreatment or chronic exposure to stress antagonised this response. After pretreatment with catecholamine depleters, α-methyl-p-tyrosine, reserpine or with adrenoceptor blockers, haloperidol and chlorpromazine, the stress-induced analgesic effect was abolished. Cyproheptadine, a serotonin antagonist, also blocked this response. The results suggest the role of brain monoamines in stress-mediated analgesia.
The discovery of a second cyclooxygenase has provided fresh impetus to the search for new anti-inflammatory drugs. The second enzyme is effectively absent from healthy tissues but its levels rise dramatically during inflammation. It can be induced in migratory cells by bacterial lipopolysaccharide, cytokines and growth factors. The constitutive cyclooxygenase-1 (COX-1) can thus be considered a "housekeeping" enzyme, in contrast to cyclooxygenase-2 (COX-2) which is activated by tissue damage. Both enzymes have a molecular weight of around 70 kDa and similar Km and Vmax values for their reaction with arachidonic acid. Several non steroid anti-inflammatory drugs which have more than 1,000 fold selectivity for COX-2 over COX-1 are in the early stages of drug development.
Two series of novel derivatives based on the thienopyrimidine and pyrimidoindole ring systems, both N-substituted in position 3, have been synthesized. The compounds were obtained by reaction of N-amino groups of 5,6-dimethyl-thieno[2,3-d]pyrimidin-2,4-dione and of 5H-pyrimido[5,4-b]indol-2,4-dione with aromatic aldehydes. Some of these substances showed an appreciable analgesic activity, a good antiinflammatory activity, a low acute toxicity with an optimal gastric tolerance.
Increasing amounts of experimental and clinical data support the role of selective cyclooxygenase (COX)-2 inhibition in anti-inflammatory processes and the involvement of COX-1 inhibition in the side effects associated with non steroidal anti-inflammatory drug use. This review will focus on the differences in the structure of the COX-1 and COX-2 molecules, particularly the active site and how they are bound by various NSAIDs to achieve COX-2 selectivity. This COX-2 selectivity will then be characterized in pharmacological assays in vitro and in animal models in vivo. Finally, clinical information available for this new class of selective inhibitors will be discussed.
Two series of N-[5-(2-furanyl)-2-methyl-4-oxo-4H-thieno[2,3-d]pyrimidin-3-yl]-carboxamide (4a-m) and 3-substituted-5-(2-furanyl)-2-methyl-3H-thieno[2,3-d]pyrimidin-4-ones (5a-m) were synthesised using appropriate synthetic route. All the test compounds 4a-m and 5a-m were assayed in vitro for antibacterial activity against two different strains of Gram-negative (Escherichia coli and S. typhi) and Gram-positive (S. aureus, B. subtilis) bacteria and the antimycobacterial activity was evaluated against M. tuberculosis and M. avium strains. The minimum inhibitory concentration (MIC) was determined for test compounds as well as for reference standards. The test compounds have shown significant antibacterial and antimycobacterial activity against all the microbial strains used, when tested in vitro. In general, along with the thienopyrimidinone ring, substituted amido or imino side chain at position 3 is essential for antimicrobial activity. Among the compounds tested, compounds 4c, 4e and 4g in N-[5-(2-furanyl)-2-methyl-4-oxo-4H-thieno[2,3-d]pyrimidin-3-yl]-carboxamide series and compounds 5c, 5e and 5g in 3-substituted-5-(2-furanyl)-2-methyl-3H-thieno[2,3-d]pyrimidin-4-ones series were found to be the most potent. Further the toxicity of most potent compounds 4c, 4e and 4g and 5c, 5e and 5g were assessed using hemolytic assay and minimal hemolytic concentration (MHCs) were determined. In general, test compounds were found to be non-toxic up to a dose level of 200 micromol L(-1) (MHC).
A series of novel 2-benzylamino-3-substituted quinazolin-4(3H)-ones have been synthesized by treating 3-amino-2-benzylamino quinazolin-4(3H)-one, with different aldehydes and ketones. The starting material 3-amino-2-benzylamino quinazolin-4(3H)-one was synthesized by nucleophilic substitution of thiomethyl group of 3-amino-2-methylthio quinazolin-4(3H)-one by benzylamine. The title compounds were investigated for analgesic and anti-inflammatory activities. All the test compounds exhibited significant analgesic activity, whereas the compound III is equipotent with diclofenac sodium. The compounds I, II and III showed more potent anti-inflammatory activity than diclofenac sodium.
A series of novel 2-substituted quinazolin-4(3H)-ones have been synthesized by condensing the aromatic primary amine of 2-substituted quinazolines with different aldehydes and ketones. The synthesized compounds were confirmed by their spectral data (IR, NMR and MS) and the purity was ascertained by elemental analysis. When these compounds were evaluated for analgesic and antiinflammatory activities, compounds I-VIII exhibited more potent analgesic activity than diclofenac sodium, while the compounds IV, V, VI and VII exhibited more potent antiinflammatory activity than diclofenac sodium. The activity values were found to be significant as compared to those of controls.
The reaction of 5-acetyl-4-aryl-3-cyano-6-methylpyridine-2(1H)-thiones (1a, b) with 4-methylphenacyl bromide, chloro-N-arylacetamides or chloroacetonitrile gave the corresponding S-substituted thiopyridines 2a-c, 4a-f and 6a-c, respectively. The latter compounds underwent intramolecular Thorpe-Ziegler cyclization to give 2-substituted 5-acetyl-3-amino-4-aryl-6-methylthieno[2,3-b]pyridines 3a-c, 5a-f and 7a-c. Compounds 5a-f and 7b, c are key intermediates in the synthesis of the target compounds. Some compounds showed remarkable antimicrobial activity.
A method is presented for measuring the edema induced by injection of 0.05 ml of 1% solution of carrageenin, an extract of Chondrus, into the plantar tissues of the hind paw of the rat. Peak edema develops within the first 3 to 4 hours, and is inhibited by pretreatment of the animals by single oral doses of antiinflammatory agents, steroid or non-steroid. Log dose responses to drugs are linear and parallel, and yield potency ratios with relatively narrow confidence limits. The potency ratios obtained for aspirin, phenylbutazone and hydrocortisone are fairly close to the ratios of their respective daily doses in the treatment of rheumatic disease. A potent antihistaminic-antiserotonin compound, cyproheptadine, is without effect on carrageenin-induced edema.
A variety of novel 2-methylthio-3-substituted quinazolin-4-(3H)-ones have been synthesized by reacting (2-methylthio-4-oxo-3H-quinazolin-3-yl)dithiocarbamic acid methyl ester with a variety of amines, the starting material dithiocarbamate was synthesized from methylanthranilate. The title compounds were investigated for analgesic, anti-inflammatory and antibacterial activities. While the test compounds exhibited significant activity, the compounds A1, A2, A3 and A4 shown more potent analgesic activity, and the compound A4 shown more potent anti-inflammatory activity than the reference diclofenac sodium.
Antiulcerogenic effect of banana have been reported from this laboratory and elsewhere but in none of these communications was the species and variety mentioned. The effects of different biological variables like size (indicating maturity), season and soil on the antiulcerogenic effect of banana have also not been reported. The data of the present study indicate that the antiulcerogenic effect of banana is present primarily in the unripe, green plantain banana obtained from plant MUSA SAPIENTUM Linn variety PARADISIACA. The antiulcerogenic principle in plantain banana appears to be present in big (mature) unripe fruits and varies from season to season and place to place in the Indian subcontinent. The antiulcerogenic principle seems to be thermolabile. Antiulcerogenic effects seems to be due to strengthening of mucosal resistance factors.
A method for determinating loss of pain sensation
- R E Amour
- D L Smith
- RE Amour
Carregeenin induced oedema in hind paw of the rat as assay for antiinflammatory drugs
- C A Winter
- E A Risely
- G W Nuss
- CA Winter