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PubMed1985

Peroxidation of liposomes promoted by human polymorphonuclear leucocytes.

Human polymorphonuclear leucocytes were found to promote peroxidation of phospholipid liposomes upon stimulation by phorbol myristate acetate. Peroxidation required the presence of either pyrophosphate-chelated or ADP-chelated iron, whereas iron chelated to EDTA or ATP had no effect. Peroxidation was also catalyzed by ferritin, but not by transferrin. Superoxide dismutase abolished the peroxidation, whereas catalase and apparently also the hydroxyl radical scavenger dimethyl sulphoxide were inactive, indicating that the peroxidation was mediated by superoxide radicals but not by hydrogen peroxide or hydroxyl radicals. Xanthine oxidase-promoted peroxidation was studied for comparison and showed similar characteristics except that transferrin catalyzed the peroxidation. Peroxidation of membrane lipids may be a mechanism whereby granulocytes cause tissue damage in inflammation. The drugs paracetamol, gentisic acid and 5-aminosalicylic acid inhibited lipid peroxidation, probably through their ability to react with the superoxide anion.

Cytochrome c Group↗
PubMed1999

Multiwavelength spectrophotometric determination of acid dissociation constants: Part II. First derivative vs. target factor analysis.

PURPOSE: Acid dissociation constants (pKa values) denote the extent of ionization of drug molecules at different pH values, which is important in understanding their penetration through biological membranes and their interaction with the receptors. However, many drug molecules are sparingly soluble in water or contain ionization centres with overlapping pKa values, making precise pKa determination difficult using conventional spectrophotometric titration. In this work, we investigate a multiwavelength spectrophotometric titration (WApH) method for the determination of pKa values. METHODS: Spectral changes which arise during pH-metric titrations of substances with concentration of about 10(-5) M were captured by means of an optical system developed in this study. All experiments were carried out in 0.15 M KCI solution at 25 +/- 0.5 degrees C. Mathematical treatments based on the first derivative spectrophotometry procedure and the target factor analysis method were applied to calculate the pKa values from the multiwavelength absorption titration data. RESULTS: pKa values were determined by the WApH technique for six ionizable substances, namely, benzoic acid, phenol, phthalic acid, nicotinic acid, p-aminosalicylic acid and phenolphthalein. CONCLUSIONS: The pKa values measured using the WApH technique are in excellent agreement with those measured pH-metrically. We have demonstrated that the first derivative spectrophometry procedure provides a relatively simple way to visualize the pKa values which are consistent with those determined using the target factor analysis method. However, for ionization systems with insufficient spectral data obtained around the sought pKa values or with closely overlapping pKa values, the target factor analysis method outperforms the first derivative procedure in terms of obtaining the results. Using the target factor analysis method, it has been shown that the two-step ionization of phenolphthalein involves a colorless anion intermediate and a red colored di-anion.

Benzoic Acid↗
PubMed2002

Dissociated ROS production and ceramide generation in sulfasalazine-induced cell death in Raw 264.7 cells.

Sulfasalazine (SSZ) is a drug used in inflammatory bowel disease, whose precise mechanism of action remains to be clarified. Here, we report that incubation of Raw 264.7 cells with SSZ but not salicylates [acetylsalicylic acid (ASA), 4-aminosalicylic acid (4-ASA), and 5-ASA] causes a mixed apoptotic and necrotic form of cell death. In contrast to its metabolites, sulfapyridine and 5-ASA, SSZ exposure in Raw 264.7 cells resulted in a threefold increase in ceramide generation, as well as a robust production of reactive oxygen species (ROS). However, inhibition of ceramide production by fumonisin B1 failed to attenuate cell death. Preincubation with catalase, cyclosporin A (CsA), and bongkrekic acid attenuated ROS production. When dead cells were quantified for apoptotic versus necrotic cell death, catalase and N-acetylcysteine reproducibly attenuated apoptosis, whereas CsA, in addition to reducing apoptosis, was observed to dramatically enhance necrosis. In conclusion, the cell-death response induced by SSZ in Raw 264.7 cells involves ROS in the apoptotic limb but is independent of ceramide formation.

Animals↗
PubMed1991

Extrahepatic expression of the N-acetylation polymorphism toward arylamine carcinogens in tumor target organs of an inbred rat model.

An N-acetylation polymorphism is described that is expressed toward arylamine carcinogens in tumor target organs of an inbred rat model. High levels (rapid acetylator phenotype) of arylamine carcinogen N-acetyltransferase activity were observed in kidney, colon, prostate and urinary bladder cytosols derived from Fischer (F-344) inbred rats, the strain most commonly used for tumor bioassay studies and the strain most particularly used in arylamine-induced colon and prostate cancer studies. Significantly lower (slow acetylator phenotype) levels of arylamine carcinogen N-acetyltransferase activity were observed in corresponding tissue cytosols derived from Wistar-Kyoto inbred rats. Intermediate levels of arylamine carcinogen N-acetyltransferase activity significantly different from both the parental strains were observed in F1 hybrids of the parental strains, consistent with codominant expression of two alleles at a single gene locus. The arylamine substrates exhibiting the acetylator phenotype-dependent N-acetyltransferase activities included p-aminobenzoic acid, p-aminosalicylic acid, p-phenetidine, p-aminophenol, 2-aminofluorene, 3,2'-dimethyl-4-aminobiphenyl, beta-naphthylamine and 4-aminobiphenyl, but not procainamide. Highest levels of arylamine carcinogen N-acetyltransferase were expressed consistently in colon cytosol, but expression of the N-acetylation polymorphism toward arylamine carcinogens was observed in each (kidney, colon, prostate and urinary bladder) of the tumor target organs. The expression of the N-acetylation polymorphism in tumor target organs suggests that the inbred rat model will be useful in assessing the role of acetylator phenotype in arylamine-induced cancers of the colon and prostate.

Acetylation↗
PubMed1991

Relative bioavailability of olsalazine from tablets and capsules: a drug targeted for local effect in the colon.

The aim of this investigation was to compare two formulations of the prodrug olsalazine (OLZ) with regard to local bioavailability of 5-aminosalicylic acid (5-ASA) in the colon. Since 5-ASA can not be measured directly in the colon, the bioavailability was evaluated by studying the plasma concentration and cumulative urinary excretion (Ae) of its main metabolite N-acetyl-5-aminosalicylic acid (ac-5-ASA). The absorption of OLZ was also studied. A single dose of 1g OLZ tablets and capsules was given to nine healthy fasting volunteers in two repeated two-period cross-over studies. Blood and urine samples were collected for 72 and 96 h, respectively. AUC, Cmax and Ae data from both studies were combined for statistical analysis. Ninety per cent confidence limits for differences in mean AUC for ac-5-ASA (tablet-capsule) compared to that of capsules were -0.31 per cent and 30.8 per cent. This indicates bioequivalence if a more relaxed criterion than the conventional +/- 20 per cent is applied, which is justified in this situation. The 90 per cent confidence limits for Cmax were -10.5 per cent and 36.9 per cent while for Ae the values were -20.5 per cent and 23.7 per cent. Within and between subject variability estimates for AUC of ac-5-ASA were 24 per cent and 46 per cent, respectively.

Adult↗
PubMed1977

The binding of antituberculous drugs to normal and kwashiorkor serum.

The protein binding of 6 antituberculous drugs--ethambutol, ethionamide, isoniazid, para-aminosalicylic acid, rifampicin and streptomycin--to normal and kwashiorkor serum has been investigated. The binding of these drugs was mildly decreased in kwashiorkor serum, but not to such an extent as to be of therapeutic importance, except for streptomycin and possibly para-aminosalicylic acid (PAS). With streptomycin there was a 15% increase in the free component in kwashiorkor serum, while with PAS there was a 12% increase in the free component. Of interest is the observation that rifampicin is predominantly bound to the gamma-globulin fraction, both in normal and in kwashiorkor serum. Secondary binding, predominantly to the alpha 1-, alpha 2-and gamma-globulin fractions, was seen quite commonly in kwashiorkor serum in association with diminished albumin binding.

Aminosalicylic Acid↗
PubMed1991

Increased activation of isolated intestinal lamina propria mononuclear cells in inflammatory bowel disease.

Normal human lamina propria lymphocytes are in a heightened state of activation compared with peripheral blood with regard to cell-surface activation antigen expression (transferrin receptor, interleukin-2 receptor, 4F2) and the increased spontaneous secretion of immunoglobulins in vitro. This study evaluates the cell-surface expression of activation-associated antigens in different subpopulations of isolated colonic lamina propria mononuclear cells in inflammatory bowel disease. In pilot studies using three-color flow cytometry, autofluorescence was observed that was emitted by unstained lamina propria mononuclear cells, which interfered with both the sensitivity and the specificity of the analyses. Because a major portion of the intestinal lymphocyte populations of interest were autofluorescent, a method to remove autofluorescence signals was developed by designing a computer program for the subtraction of autofluorescence from the emissions of each individual cell. This technique increases both the sensitivity and specificity of flow-cytometric analyses of intestinal lamina propria mononuclear cells. Using fluorescence-activated cell-sorter analyses with subtraction of autofluorescence on a single-cell basis, increased expression of lymphocyte activation antigens (interleukin-2 receptor, transferrin receptor, 4F2) was found on the cell surface of isolated intestinal B cells, T cells, CD4+ T cells, and CD8+ T cells in both Crohn's disease and ulcerative colitis. Therefore, markedly increased intestinal lymphocyte activation is a major immunological alteration in inflammatory bowel disease and includes all lymphocyte subpopulations investigated in this study. In addition, 5-aminosalicylic acid, which is used for the treatment of intestinal inflammation in inflammatory bowel disease, inhibits the expression of cell-surface activation antigens on mitogen-activated peripheral blood lymphocytes in a dose-dependent manner. These observations suggest that lymphocyte activation may play an important role in underlying immune processes that lead to chronicity and perpetuation of inflammatory bowel disease and may implicate an additional mechanism for the therapeutic action of 5-aminosalicylic acid.

Aminosalicylic Acids↗
PubMed2002

Study of the plasma pharmacokinetics and faecal excretion of the prodrug olsalazine and its metabolites after oral administration to horses.

Olsalazine sodium (Dipentum*) has been used therapeutically against inflammatory bowel disease in human medicine as an alternative to sulphasalazine over the past 20 years. Bacteria in the colon split this prodrug into two molecules of the locally effective 5-aminosalicylic acid (5-ASA). Considering the potential therapeutic use in equine colitis, the pharmacokinetics of olsalazine (OLZ) after single oral administration to six horses at a dosage of 30 mg/kg was investigated. Plasma concentrations of OLZ, 5-ASA, and its main metabolite N-acetyl-5-aminosalicylic acid (Ac-5-ASA) were analysed by high-performance liquid chromatography methods. Evaluation of the plasma pharmacokinetics revealed a rapid, but low extent of absorption of OLZ (peak concentrations around 1 microg/mL at 0.5-1.5 h), and a delayed minimal absorption of 5-ASA (concentrations < 0.2 microg/mL, at 11-35 h), which is immediately metabolized to Ac-5-ASA. As indicators of the local availability in the colon, high faecal water concentrations of 5-ASA and Ac-5-ASA (mean C(max) about 300 and 130 microg/mL, respectively), but only traces of OLZ were found in faeces excreted 18-50 h after dosing. Of the administered OLZ dose 26% could be recovered from faeces, almost completely as 5-ASA and Ac-5-ASA. Routine clinical examination of the horses and assay of standard haematological and serum chemistry parameters before and after OLZ administration confirmed that a single dosage of 30 mg/kg was well tolerated. To estimate the systemic availability of 5-ASA liberated from OLZ, 5-ASA was administered i.v. at a dosage of 1.5 mg/kg to four horses and plasma concentrations of 5-ASA and Ac-5-ASA were determined. The pharmacokinetic evaluation showed a very low bioavailability of 2.4% for 5-ASA, released from orally administered OLZ. Furthermore, in an in vitro experiment, the metabolic transformation of 5-ASA to Ac-5-ASA mediated by bacteria in the caecal content of horses was determined at 38 degrees C for 31 h and compared with the metabolism data of the in vivo study. The markedly lower degree of acetylation in vitro supports the assumption that biotransformation of 5-ASA in vivo occurs not only by colonic bacteria, but also at other sites.

Administration, Oral↗
PubMed1976

Cholestyramine-induced inhibition of salicylazosulfapyridine (sulfasalazine) metabolism by rat intestinal microflora.

The effect of multiple oral administration of the hypocholesterolemic agent cholestyramine (a strongly basic anion-exchange resin) on the metabolism of salicylazosulfapyridine by microflora present in the colon and cecum was assessed in conventional rats by following the time course of salicylazosulfapyridine and its metabolites in the urine and feces. The intestinal metabolism of salicylazosulfapyridine (a single 100 mg/kg oral dose), which involves reduction of the azo linkage by bacterial azo reductases and the liberation of sulfapyridine and 5-aminosalicylic acid (potential active metabolites of the drug), was markedly inhibited by the resin (250 mg/kg oral doses at -2, +2 and +6 hours), resulting in an enhanced fecal excretion of intact salicylazosulfapyridine. The existence of a rank-order correlation between the in vitro binding of salicylazosulfapyridine, sulfapyridine and 5-aminosalicylic acid to the resin and their fecal excretion pattern in resin-treated animals suggests that a direct cholestyramine-salicylazosulfapyridine interaction occurred within the intestinal tract and that in the bound state, the azo bond of the drug was inaccessible to bacterial azo reductases. These findings suggest that chronic oral administration of cholestyramine to patients with ulcerative colitis who are receiving salicylazosulfapyridine could result in a significant reduction in the absorption and metabolism of the drug and hence, in its therapeutic efficacy.

Aminosalicylic Acids↗
PubMed2005

Inhibition of Clostridium difficile toxin A-induced colitis in rats by APAZA.

A new compound, APAZA, consisting of a molecule of 5-aminosalicylic acid linked to one molecule of 4-aminophenylacetic acid by an azo bond, was testedfor its ability to inhibit acute colitis in rats caused by Clostridium difficile toxin A. When administered chronically for 5 days in drinking water, APAZA significantly inhibited toxin A-induced myeloperoxidase activity, luminal fluid accumulation, and structural damage to the colon at doses of from 1 to 100 mg/kg x day. For comparison, sulfasalazine was administered in identical doses and was found to significantly inhibit toxin A-induced colitis only at the dose of 100 mg/kg x day. When 4-aminophenylacetic acid alone was administered chronically in drinking water, it also inhibited toxin A-induced colonic inflammation at a dose of 100 mg/kg x day. In order to determine if 4-aminophenylacetic acid has a direct anti-inflammatory effect on the colon rather than a systemic effect, 4-aminophenylacetic acid was administered acutely to surgically prepared isolated colonic segments by intraluminal injection in anesthetized rats 30 min before toxin A was injected. 4-Aminophenylacetic acid strongly and significantly inhibited toxin A-induced colitis in this experiment at doses as low as 10 microg/segment. It is concluded that APAZA is a potent inhibitor of toxin A-induced colonic inflammation in rats and that its constituent, 4-aminophenylacetic acid, is responsible for this increased protection against colitis compared to the 5-aminosalicylic acid component of sulfasalazine.

Analysis of Variance↗
PubMed1959

Diagnosis and treatment of joint tuberculosis.

Tuberculosis of the joints is not a clinical oddity and a diagnosis of tuberculous infection must be considered in all joint lesions if diagnosis is to be made early. A history of insidious onset of pain, especially if accompanied by pulmonary symptoms or a history of contact with a tuberculous person, should alert the clinician to the possibility of this diagnosis. The tuberculin test, roentgenograms, culture of aspirated fluids and biopsy, by anthrotomy or punch, continue to be the standard procedures for establishing the diagnosis. The differential diagnosis must include the entire gamut of bone and joint disease. Chemotherapy combining streptomycin and dihydrostreptomycin with isonicotinic acid hydrazid and para-aminosalicylic acid is of extreme value in the eradication of draining sinuses and in the advancement of the ideal surgical date; but general physical and mental hygiene, rest and the prevention or correction of deformities is a continuing therapeutic necessity. Fusion of the affected area is advocated in almost all lesions although there is some hope that functioning joints may be preserved with early diagnosis, conservative surgical treatment and more efficient antibiotics. A postoperative regime similar to the preoperative treatment must be continued until the stabilization is firm or until there is no evidence of activity.

Aminosalicylic Acid↗
PubMed2002

Melatonin reduces colon immunological injury in rats by regulating activity of macrophages.

AIM: To investigate the effects of melatonin on the colon immunological injury of rats and the role of macrophages in this process. METHODS: The rats colitis was established by intrarectal injection with 2,4,6-trinitrobenzenesulfonic acid (TNBS) and ethanol. The animals were randomized into 6 groups: normal group, model group, 5-aminosalicylic acid group (100 mg/kg), and melatonin group (2.5, 5.0, and 10.0 mg/kg), treated intrarectally with saline, saline, 5-aminosalicylic acid, and melatonin, respectively (once a day, from d 7 after colitis established to d 28). At the end of the experiment, the colon mucosa damage index (CMDI), the score of histology (HS), the level of myeloperoxidase(MPO), and the sore of occult blood test (OBT) were evaluated. Meanwhile, the activity of interleukin-1 (IL-1), tumour necrosis factor-alpha (TNF-alpha, and nitric oxide (NO) were also detected. RESULTS: After treated with TNBS and ethanol, the extents of CMDI, HS, OBT, and the level of MPO in model group were more higher than that in normal group. Melatonin could alleviate the colon injury, and reduce the level of MPO and the degree of OBT. The activity of IL-1, TNF-alpha, and NO which released mainly from macrophages was elevated remarkably. Melatonin could depress all this parameters. CONCLUSION: Melatonin could reduce the colon damage in the colitis rats by regulating macrophage activity.

Animals↗
PubMed1982

The influence of metabolic variation on analgesic nephrotoxicity. Experiments with the Gunn rat.

The analgesics aspirin and paracetamol administered as single I.V. doses produce renal lesions in the homozygous Gunn rat. The lesions affect both cortex and medulla but are less severe than the renal lesions of analgesic nephropathy. By contrast the reactive compounds p-aminophenol and 5-aminosalicylic acid which are known to cause renal damage in other less susceptible strains respectively produce cortical and medullary renal lesions in homozygous Gunn rats which are as extensive as those found in patients with analgesic nephropathy. The increased frequency of renal lesions from the analgesics aspirin and paracetamol as compared to heterozygous and albino rats and the increased severity of the lesions due to p-aminophenol and 5-aminosalicylic acid is considered to be at least partly due to impaired glucuronide formation and consequent delayed excretion of nephrotoxic substances.

Acetaminophen↗
PubMed1987

Sulphasalazine induced seminal abnormalities in ulcerative colitis: results of mesalazine substitution.

Seminal abnormalities are commonly found during sulphasalazine treatment. Although these changes appear reversible after drug withdrawal this may result in colitis relapse. Animal studies suggest that 5-aminosalicylic acid, the active component of sulphasalazine, does not impair fertility. Sixteen patients with quiescent ulcerative colitis were studied. Each patient produced three samples of semen at weekly intervals. Of the 48 samples analysed 39.6% showed oligospermia, 41.7% showed an increased number of abnormal forms and 91.7% showed impaired motility. Nine patients substituted enteric coated mesalazine (5-aminosalicylic acid) for sulphasalazine for a minimum period of three months. During this time one patient developed a salmonella associated colitis relapse; the others remained well. Improvement in sperm count (p less than 0.02), motility (p less than 0.001) and morphology (p less than 0.02) occurred in all cases. To date, four successful pregnancies have resulted, three in couples complaining of long term infertility. Treatment with enteric-coated mesalazine allows the recovery of seminal abnormalities induced by sulphasalazine in patients with colitis.

Adult↗
PubMed2003

Protective effect of angelica sinensis polysaccharide on experimental immunological colon injury in rats.

AIM: To study the effect of angelica sinensis polysaccharide (ASP) on immunological colon injury and its mechanisms in rats. METHODS: Immunological colitis model of rats was induced by intracolon enema with 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) and ethanol. The experimental animals were randomly divided into normal control, model control, 5-aminosalicylic acid therapy groups and three doses of ASP therapy groups. The 6 groups were treated intracolonically with normal saline, normal saline, 5-aminosalicylic acid (100 mg.kg(-1)), and ASP daily (8:00 am) at the doses of 200, 400 and 800 mg.kg(-1) respectively for 21 days 7 d following induction of colitis. The rat colon mucosa damage index (CMDI), the histopathological score (HS), the score of occult blood test (OBT), and the colonic MPO activity were evaluated. The levels of SOD, MDA, NO, TNF-alpha, IL-2 and IL-10 in colonic tissues were detected biochemically and immunoradiometrically. The expressions of TGF-beta and EGF in colonic tissues were also determined immunochemically. RESULTS: Enhanced colonic mucosal injury, inflammatory response and oxidative stress were observed in colitis rats, which manifested as significant increases of CMDI, HS, OBT, MPO activity, MDA and NO contents, as well as the levels of TNF-alpha and IL-2 in colonic tissues, although colonic TGF-beta protein expression, SOD activity and IL-10 content were significantly decreased compared with the normal control (P<0.01). However, these parameters were found to be significantly ameliorated in colitis rats treated intracolonically with ASP at the doses of 400 and 800 mg.kg(-1) (P<0.05-0.01). Meantime, colonic EGF protein expression in colitis rats was remarkably up-regulated. CONCLUSION: ASP has a protective effect on immunological colon injury induced by TNBS and ethanol enema in rats, which was probably due to the mechanism of antioxidation, immunomodulation and promotion of wound repair.

Angelica sinensis↗
PubMed1994

Pharmacokinetic studies of benzalazine.

The pharmacokinetic properties of benzalazine ((2-hydroxy-5-[(4-carboxyphenyl)azo]benzoic acid, CAS 64896-26-0), a new agent for the treatment of ulcerative colitis and Crohn's disease of the large intestine, were investigated. From jejunal loops of rats in situ no noteworthy absorption of benzalazine was observed. All attempts to demonstrate metabolic conversion of benzalazine in mucosal homogenate of the small intestine of rats were without any success. In faecal suspensions, the half-life of the metabolic conversion of benzalazine was determined as 15 min and the formation of the metabolite 5-aminosalicylic acid (5-ASA) was demonstrated qualitatively. 72 h after single oral administration of 300 mg benzalazine/kg b.w. to rats, an average of 71.83% of the administered dose was recovered in urine and faeces. Only a small amount of unmetabolized benzalazine was excreted with urine and faeces (0.75% and 1.47% of the administered dose, respectively). The benzalazine metabolite 5-ASA and the 5-ASA metabolite acetyl-5-aminosalicylic acid (Ac-5-ASA) were excreted mainly with the faeces (29.22% and 20.66% of the administered dose, respectively) and only in small amounts with the urine (2.54% and 11.06% of the administered dose, respectively).

Aminosalicylic Acids↗
PubMed2002

Immobilization of a nonsteroidal antiinflammatory drug onto commercial segmented polyurethane surface to improve haemocompatibility properties.

A method has been developed in which a layer of p-aminosalicylic acid (4-amino-2-hydroxybenzoic acid) (PAS), a water soluble pharmaceutical compound of the nonsteroidal anti-inflammatory drug (NSAID) class with antiaggregant platelet activity, is covalently immobilized onto a segmented polyurethane, Biospan (SPU) surface. Thus, SPU surfaces were modified by grafting of hexamethylenediisocyanate. and the free isocyanate remaining on the SPU surface were then coupled through a condensation reaction to amine groups of p-aminosalicylic acid. The bonding of PAS from aqueous solution onto SPU surface was studied by ATR-FTIR. UV and fluorescence spectroscopy. Plateau levels of coupled PAS were reached within 1.2 microg/cm2 using PAS solution concentrations of 1mg/ ml. The surface wettability of the polymeric films measured by contact angle indicate that the introduction of the PAS turns the surface more hydrophilic (theta(water) = 43.1 +/- 2.1) relatively to the original SPU films (theta(water) = 70.3 +/- 1.9). The in vitro albumin (BSA) adsorption shows that the PAS-SPU films adsorb more BSA (250/microgmm2) than the original SPU (112 microg mm2). Thrombogenicity was assessed by measuring the thrombus formation and platelet adhesion of the SPU containing PAS relatively to nonmodified SPU surfaces. The polymeric surfaces with immobilized PAS had better nonthrombogenic characteristics as indicated by the low platelet adhesion, high adsorption of albumin relatively to fibrinogen and low thrombus formation, making them potentially good candidates for biomedical applications.

Albumins↗
PubMed1985

[Biological effects of new PAS derivatives on Mycobacterium tuberculosis].

A new series of p-aminosalicylic acid derivatives were tested in vitro against Myc.tbc. H37Rv strain and clinically isolated pathogenic mycobacteria. 4 - [alpha - (benzylamino - thiocarbonylthio) - acetamido] - salicylic acid was most active, 4 - [alpha - methyl - alpha - (furfurylamino - thiocarbonylthio) - acetamido] - salicylic acid was more active than PAS. 4 - [alpha - (ethylamino - thiocarbonylthio) - acetamido] - salicylic acid, and 4 - [alpha - methyl - alpha - (ethylamino - thiocarbonylthio) - acetamido] - salicylic acid derivatives were nearly as active as PAS. The causes of increase in tuberculostatic activity can be assumed to be the isothiocyanate groups, which are the products of hydrolysis of the compounds investigated.

Aminosalicylic Acid↗