Showing papers in "Archiv Der Pharmazie in 2001"
TL;DR: Among these compounds the zirconium complex of mendiaxon showed highest cytotoxic activity against human promyelocytic leukemic HL‐60 cells, and the inorganic salt was found to be active against this cell line.
Abstract: Zirconium complexes of mendiaxon, warfarin, coumachlor, and niffcoumar have been synthesized by reaction of the ligands with zirconium chloride in stoichiometric ratio 1:2. The formation of the complexes has been proved on the basis of elemental analysis, IR-spectroscopy, 1H-NMR spectroscopy, and thermal studies. Differential thermal analyses and thermogravimetric analyses have been applied to study the compositions of the new complexes. It is concluded that the lactone- and the keto-carbonyl groups of warfarin, coumachlor, and niffcoumar are bonded to the metal ion as bidentate ligands, but mendiaxon is bonded as monodentate ligand. Cytotoxic screening by MTT-assay was carried out. Among these compounds the zirconium complex of mendiaxon showed highest cytotoxic activity against human promyelocytic leukemic HL-60 cells. The inorganic salt was found to be active against this cell line.
65 citations
TL;DR: It was found that acylation of 6‐(1‐hydroxyalkyl)‐ DMNQ derivatives possessing alkyl chains of C2‐C5 enhanced both bioactivities, suggesting that an increase of electrophilicity in the quinoid moiety makes the electrophilic arylation of bionucleophiles more favorable.
Abstract: 2- or 6-(1-Hydroxyiminoalkyl)-5,8-dimethoxy-1,4-naphthoquin-one (DMNQ) and 6-(1-propyloxyimino- alkyl)-DMNQ derivatives were synthesized, and their inhibitory effects on DNA topoisomerase-I (TOPO-I) and antiproliferative activities against L1210 cells were examined. In a comparison, it was found that 6-(1-hydroxyiminoalkyl)-DMNQ derivatives exhibited higher potencies in both bioactivities than 2-(1-hydroxyiminoalkyl)-DMNQ analogues, suggesting that the difference in bioactivities between two positional isomers might be due to the steric hindrance of the side chain. It is noteworthy that the optimal size of alkyl group for both bioactivities of 6-(1-hydroxyiminoalkyl)-DMNQ derivatives was pentyl to octyl (IC50, 22-29 microM) for the inhibition of TOPO-I and propyl to nonyl (ED50, 0.12-0.19 microM) for the antiproliferative activity. In addition, a similar potency of bioactivities was expressed by 6-(1-propyloxyiminoalkyl)-DMNQ derivatives, propylation products of the oximes.
46 citations
45 citations
TL;DR: G glycine‐derived amides showed a higher activity than the β‐alanine and GABA derivatives in the maximal electroshock seizure (MES) test in mice upon intraperitoneal administration and might represent promising antiepileptic drugs.
Abstract: In order to study the influence of the length of the amino acid chain of N,N-phthaloyl-amino acid amides as analogues of the former anticonvulsant taltrimide on the seizure-antagonizing activity glycine, beta -alanine and gamma -aminobutyric acid (GABA) derivatives were synthesized. The corresponding taurine derivatives were also included. Generally, the glycine-derived amides showed a higher activity than the beta -alanine and GABA derivatives in the maximal electroshock seizure (MES) test in mice upon intraperitoneal administration. The activity was comparable to the respective taurine derivatives. The N,N-phthaloyl-glycine, amides were also active in the MES test upon oral administration to rats. No significant activity was noted in the seizure threshold test with subcutaneous pentylenetetrazole. The ED50 of N,N-phthaloyl-glycine ethyl amide (4b) in the MES test upon intraperitoneal administration to mice was 19.1 mg/kg. On a molar basis this activity is comparable to the activity of phenytoin with little toxicity in the rotorod test. In conclusion, N,N-phthaloyl-glycine amides might represent promising antiepileptic drugs.
45 citations
TL;DR: In this article, pyrazolo[3,4b]quinoline derivatives have been prepared by cyclization of the intermediate 2-chloroquinoline-3-carbonitrile.
Abstract: New pyrazolo[3,4-b]quinoline derivatives have been prepared by cyclization of the intermediate 2-chloroquinoline-3-carbonitrile 7, namely 3-amino-1H-pyrazolo[3,4-b]quinoline 8a, 3-amino-1-phenyl/(p-substituted)phenyl/-1H-pyrazolo[3,4-b]-quinoline 8b-f. Furthermore, 3-[(3-aryl-4-oxothiazolidin-2-ylidene)amino]-1H-pyrazolo[3,4-b]quinolines 11a,b; 3-[(3-aryl-4-oxothiazin-2-ylidene)amino]-1H-pyrazolo[3,4-b]quinolines 12a,b and 3-(2-aryl-4-oxothiazolidin-3-yl)-1H-pyrazolo[3,4-b]quinolines 13a,b were synthesized. The antimicrobial activity was evaluated for most of the prepared compounds.
43 citations
TL;DR: The antibacterial and antifungal activities of the novel compounds against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Shigella flexneri and Proteus mirabilis were tested and the minimal inhibitory concentrations of these compounds were determined using the micro dilution method.
Abstract: 5-Phenyl/methyl-5-morpholinomethyl/pyrrolidinomethyl-2-(5- aryl-1,3,4-oxadiazol-2-yl)imino]-4-thiazolidinones (5a-m) were synthesized by the reaction of 5-phenyl/methyl-2-[(5-aryl-1,3,4-oxadiazol -2-yl)imino]-4-thiazolidinones (4a-j) with formaldehyde and morpholine or pyrrolidine. The structures of the compounds were determined by analytical and spectral (IR, 1H-NMR, EIMS) methods. The antibacterial activities of the novel compounds against Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC 8739, Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 1539, Salmonella typhi, Shigella flexneri and Proteus mirabilis and antifungal activity against Candida albicans ATCC 10231 were tested using the disk diffusion method. Compounds 5a, 5b, 5c, 5e, 5g, and 5h were found to be active against S. aureus ATCC 6538 (MIC: 312.5; 39; 19.5; 39; 156; and 78 micrograms/mL respectively) and compounds 5c and 5h against S. flexneri (MIC: both 312.5 micrograms/mL). The minimal inhibitory concentrations of these compounds were determined using the micro dilution method.
39 citations
TL;DR: The micelle‐forming copolymer of poly(ethylene glycol)‐ poly(aspartic acid) prodrug with isoniazid was synthesized and was found to be active in Mycobacterium tuberculosis culture, with a minimal inhibitory concentration 5.6 times lower than that of the tuberculostatic drug.
Abstract: With the objective of obtaining slow-acting isoniazid derivatives, of potential use as chemoprophylactics or chemotherapeutics in tuberculosis, the micelle-forming copolymer of poly(ethylene glycol)-poly(aspartic acid) prodrug with isoniazid was synthesized. The derivative obtained was found to be active in Mycobacterium tuberculosis culture, with a minimal inhibitory concentration (MIC) 5.6 times lower than that of the tuberculostatic drug.
39 citations
TL;DR: 3,4‐Dichlorochalcone was the most effective compound, and was also studied in another model of pain in mice, the formalin test, where it inhibited only the inflammatory pain (second phase), being equipotent to the reference drugs.
Abstract: Eleven chalcones were prepared and tested as antinociceptive agents using the writhing test in mice. Some compounds, given intraperitoneally, caused potent and dose-related antinociception, being several times more active than some reference drugs. The results evidenced that some physico-chemical parameters are involved in the pharmacological activity. 3,4-Dichlorochalcone (2) was the most effective compound, and was also studied in another model of pain in mice, the formalin test. Here it inhibited only the inflammatory pain (second phase), being equipotent to the reference drugs.
38 citations
TL;DR: A new series of arylidene 5‐phenyl‐4‐R‐pyrrole‐3‐carbohydrazides 1a—j were prepared and evaluated for their analgesic‐antiinflammatory activities and were found to be more potent as antinociceptive agents respect to dipyrone and indometacin, used as reference drugs.
Abstract: A new series of arylidene 5-phenyl-4-R-pyrrole-3-carbohydrazides 1a—j were prepared and evaluated for their analgesic-antiinflammatory activities. All synthesized compounds showed a significant analgesic action in mice after intraperitoneal administration at a dose of 100 μM/kg. Two of these, 1b , (4'-methylbenzylidene)-5-phenyl-1 H -pyrrole-3-carbohydrazide, and 1d , (4'-chlorobenzylidene)-5-phenyl-1 H -pyrrole-3-carbohydrazide, were found to be more potent as antinociceptive agents respect to dipyrone and indometacin, used as reference drugs. Among compounds 1 , only 1b showed a moderate antiinflammatory effect in rats while 1d proved to be a potent non antiinflammatory analgesic.
37 citations
TL;DR: Some 1H‐benzimidazole‐carboxamide derivatives were prepared and their antimicrobial activities against Staphyloccus aureus, Escherichia coli and Candida albicans evaluated and compounds 18, 22, and 25 exhibited the best activity against CandidaAlbicans.
Abstract: Some 1H-benzimidazole-carboxamide derivatives were prepared and their antimicrobial activities against Staphyloccus aureus, Escherichia coli and Candida albicans evaluated. Compounds 18, 22, and 25 exhibited the best activity against Candida albicans.
36 citations
TL;DR: The synthesis and pharmacological evaluation of new [(2‐oxobenzothiazolin‐3‐yl)‐methyl]‐ 4‐alkyl/aryl‐1,2,4‐triazoline‐5‐thiones are reported and on the basis of available data the structure‐activity relationship in the compounds was discussed.
Abstract: The synthesis and pharmacological evaluation of new [(2-oxobenzothiazolin-3-yl)-methyl]- 4-alkyl/aryl-1,2,4-triazoline-5-thiones are reported. All compounds were screened for analgesic and antiinflammatory activities by using the AcOH induced-stretching test, the hot plate test, the tail clip test, and the tail flick test. All of the title compounds showed more potent activity than the standard compound aspirin in the AcOH induced-stretching test. In the hot plate test [(2-oxobenzothiazolin-3-yl)methyl]-4-phenethyl-1,2,4-triazoline-5-thione 5j were revealed to be two-fold more potent in antinociceptive activity than novalgine. However, in the tail flick and tail clip test none of the compounds showed an antinociceptive activity as high as that of novalgine. On the basis of available data the structure-activity relationship in the [(2-oxobenzothiazolin-3-yl)methyl]-4-alkyl/aryl-1,2,4-triazoline-5-thiones was also discussed.
TL;DR: Benzodiazepines 1—6 were evaluated for antiproliferative activity in vitro and exhibited cytotoxic activity against human cancer cell lines, namely SW707 (colon cancer), MCF‐7 (breast cancer), A549 (lung cancer), and HCV29T (bladder cancer).
Abstract: The reaction of 2,2,4-trimethyl-1H-2,3-dihydro-1,5-benzodiazepine (1) with cinnamoyl chloride leading to the formation of 1-cinnamoyl derivative 2 is described. Two novel benzodiazepines, 2,2,4-trimethyl-1H-2,3,4,5-tetrahydro-1,5-benzodiazepine (3) and 1-cinnamoyl-2,2,4-trimethyl-1H-2,3,4,5-tetrahydro-1,5-benzodiazepine (4), were synthesized by the reduction of 1 and 2 using NaBH4 in i-PrOH and two other derivatives 5 and 6 were obtained by reaction of 4 with equimolar and dimolar quantity of cinnamoyl chloride, respectively. The structures of 1-6 were confirmed by analytical and spectral data (IR, 1H NMR, and MS). 7-Carboxy-2,2,4-trimethyl-1H-2,3-dihydro-1,5-benzodiazepine (7) was synthesized and its crystals were subjected to X-ray analysis. Benzodiazepines 1-6 were evaluated for antiproliferative activity in vitro. Among the compounds tested, 4-6 exhibited cytotoxic activity against human cancer cell lines, namely SW707 (colon cancer), MCF-7 (breast cancer), A549 (lung cancer), and HCV29T (bladder cancer).
TL;DR: Two newly synthesized compounds possess highly alkylating activity toward standard derivative 4‐(4'‐nitrobenzyl)pyridine (NBP) and four of seventeen tested compounds exhibit detectable activity against S. aureus.
Abstract: Dimethyl 2,6-dimethyl-4-oxo-4H-chromen-3-yl-phosphonate (1a) and dimethyl 6-methyl-2-phenyl-4-oxo-4H-chromen-3-yl-phosphonate (1b) were synthesized and reacted with primary aliphatic amines to yield title compounds 4-6. Their antibacterial properties against Gram-positive and Gram-negative bacteria strains were tested by the MIC method. Four of seventeen tested compounds (1d, 3, 4a, and 4b) exhibit detectable activity against S. aureus. Some representative examples of newly synthesized compounds were tested for their alkylating properties in vitro in the Preussmann test. Compounds 1a, 1c, 1d, 3, 5d, and 6a possess highly alkylating activity toward standard derivative 4-(4'-nitrobenzyl)pyridine (NBP).
TL;DR: The result showed that the presence of two quaternary ammonium cations and the distance between them are very important for the activities of the salts.
Abstract: A series of diquaternary dipiperazinium salts containing dithiocarboxyl groups 6a-f and 9 were synthesized and evaluated for their analgesic and sedative activities. The result showed that the presence of two quaternary ammonium cations and the distance between them are very important for the activities of the salts. Compound 6b exhibited the best activities (at dose 2 mg/kg, analgesic, 57%; sedative, 59%) among compounds 6a-f. Compound 9 not only showed the most potent analgesic (85.4%, dose 1 mg/kg) and sedative (93.1%, dose 1 mg/kg) activities, but also exhibited anticancer activity against KB (68.7%, dose 10 microM).
TL;DR: Nine new 3,3'‐ethylenebis(5‐alkyl‐1,3,5‐thiadiazine‐2‐thiones) were synthesized by the reaction of ethylene diamine, carbon disulfide, formaldehyde, and the appropriate alkyl amine and exhibited varied inhibitory effects on growth or sporulation of some tested fungal species.
Abstract: In a search for promising antifungal compounds, nine new 3,3'-ethylenebis(5-alkyl-1,3,5-thiadiazine-2-thiones) were synthesized by the reaction of ethylene diamine, carbon disulfide, formaldehyde, and the appropriate alkyl amine. The title compounds were tested for their antifungal activity in vitro against pathogenic (Trichophyton rubrum and Candida albicans), phytopathogenic (Penicillum expansum, Trichoderma hazianum, and Fasarium oxysporum), and aflatoxin producing (Aspergillus flavus) fungi. These compounds exhibited varied inhibitory effects on growth or sporulation of some tested fungal species.
TL;DR: Several compound exhibit profound inhibition of lipid peroxidation in vitro, including pyrrolo[1,2‐b]pyridazine 5‐position, which was induced by ascorbic acid/FeSO4 and thiobarbituric acid reactive material.
Abstract: Synthesis of 5-substituted pyrrolo[1,2-b]pyridazines with antioxidant properties. Ostby OB, Gundersen LL, Rise F, Antonsen O, Fosnes K, Larsen V, Bast A, Custers I, Haenen GR. Department of Chemistry, University of Oslo, P.O. Box 1033, Blindern, N-0315 Oslo, Norway. 5-Substituted pyrrolo[1,2-b]pyridazines have been prepared by cyclisation of pyridazine with diphenylcyclopropenone followed by further functionalisations in the pyrrolo[1,2-b]pyridazine 5-position. Several compound exhibit profound inhibition of lipid peroxidation in vitro. Lipid peroxidation of boiled rat liver microsomes was induced by ascorbic acid/FeSO4 and the peroxidation was determined by measuring the thiobarbituric acid reactive material
TL;DR: The synthesis of several new pyrazolo[3,4-b]pyridine derivatives is described in this article, and the obtained compounds were tested for their antiproliferative activity in vitro.
Abstract: The synthesis of several new pyrazolo[3,4-b]pyridine, pyrido[2',3':3,4]-pyrazolo[1,5-a]pyrimidine and imidazo[1',2':1,5]pyrazolo[3,4-b]pyridine derivatives is described The obtained compounds were tested for their antiproliferative activity in vitro One of them, 4-phenyl-2-(3,4,5-trimethoxy-beta-styrylo)pyrido- [2',3':3,4]pyrazolo[1,5-a]pyrimidine (9), revealed cytotoxic properties against the cells of all three human cancer cell lines applied Another one, 2,4-dimethyl-pyrido[2',3':3,4]pyrazolo[1,5-a]-pyrimidine (2), revealed weak cytotoxic activity only against the cells of human bladder cancer cell line HCV29T All other compounds tested did not reveal any cytotoxic activity
TL;DR: Some 5‐fluoro‐6‐substitute‐1 H‐benzimidazole‐2‐carbamates and derivatives were synthesized, and their antimicrobial and antifungal activities evaluated, and compound 12c exhibited the best activity against Candida albicans.
Abstract: Some 5-fluoro-6-substitute-1H-benzimidazole-2-carbamates (12a‐e), 5-fluoro-6-substituted 1H-benzimidazole-2-acetate (13a‐e) and 2-acetamide (14a‐f) derivatives, 2acetamido-5-fluoro-6-(morpholin-4-yl)-1-propyl-1H-benzimidazole (15), and 1-cyclopropyl-2-ethyl-5-fluoro-6-(4-methylpiperazin-1-yl)-1H-benzimidazole (16) were synthesized, and their antimicrobial and antifungal activities evaluated. Compound 12c exhibited the best activity against Candida albicans.
TL;DR: A series of 1H,3H‐thiazolo[3,4‐a]benzimidazoles were synthesized and tested for their in vitro antitumour activity against 60 human tumour cell lines and some derivatives exhibited both tumour growth inhibition activity and cellular selectivity.
Abstract: A series of 1H,3H-thiazolo[3,4-a]benzimidazoles were synthesized and tested for their in vitro antitumour activity against 60 human tumour cell lines. Some derivatives exhibited both tumour growth inhibition activity and cellular selectivity. In particular, compound 8c, the most active of the series, was very active towards all cell lines at concentrations ranging from 10(-7)-10(-5) M. Compound 4a, on the other hand, was highly selective against the CNS cancer cell line.
TL;DR: A non-isotopic histone deacetylase (HDAC) detection using a fluorescent derivative of epsilon-acetyl lysine was proposed in this article.
Abstract: The determination of the activity of histone deacetylase (HDAC) and the potency of its inhibitors has become an important goal in medicinal chemistry. This is due both to the involvement of HDAC in gene regulation and the ability of its inhibitors to modulate transcription and induce differentiation and/or apoptosis in cancer cells. We have previously reported the development of a non-isotopic assay for HDAC using a fluorescent derivative of epsilon-acetyl lysine. It can replace existing methods that rely on radioactively labeled histones or oligopeptides as substrates. Here we report validation and improvement of the procedure using an internal standard for the quantitation of the fluorescent substrate by HPLC.
TL;DR: In the course of a natural product screening for inhibitors of fungal topoisomerase 1 (TOPO 1), extracts from the actinomycete strains WS 1410 and BS 1465 exhibited promising activities, and the novel cyclo‐homononactic acid and cyclo-nonactic acid showed higher selectivity towards the wild type strain.
Abstract: In the course of a natural product screening for inhibitors of fungal topoisomerase 1 (TOPO 1), extracts from the actinomycete strains WS 1410 and BS 1465 exhibited promising activities. Bioguided fractionation of the culture broth by preparative HPLC methods yielded the collismycins A (1) and B (2) as active principles of strain WS 1410. Out of the mycelial extracts of strain BS 1465 the bioactive new natural products, cyclo-homononactic acid (3) and cyclo-nonactic acid (5) and the structurally related but inactive homononactic acid (4), were isolated. Both collismycin isomers inhibited the recombinant yeast strains ScAL 141 and ScAL 143 (TOPO 1 deletion mutant) in a non-specific manner with an MIC in the range of 2 micrograms/ml. The novel cyclo-homononactic acid (3) and cyclo-nonactic acid (5) showed higher selectivity towards the wild type strain (MIC = 2 micrograms/ml as compared to 10 micrograms/ml for the deletion mutant). All compounds obviously address a target other than TOPO 1 since they do not exhibit activities in a concurrent TOPO 1 enzyme assay.
TL;DR: Binding affinities of prepared compounds for the cloned human muscarinic M1 receptor (h‐M1) were determined by radioligand binding assay using [3H]‐N‐methylscopolamine (NMS).
Abstract: 3-Methyl-1,2,3,4-tetrahydropyrimidine-5-carbaldehyde O-substituted oximes 4 and 1-(3-methyl-1,2,3,4-tetrahydropyrimidin-5-yl)ethanone O-substituted oximes 9 have been prepared as bioisosteric congeners of arecoline which is a muscarinic agonist for treatment of Alzheimer's disease. Starting from pyrimidine-5-carbaldehyde 1, formation of the 3-methylpyrimidinium salt and subsequent reduction afforded 1,2,3,4-tetrahydropyrimidine derivatives which were converted into oxalate salts in the interest of purity and stability. Binding affinities of prepared compounds for the cloned human muscarinic M1 receptor (h-M1) were determined by radioligand binding assay using [3H]-N-methylscopolamine (NMS).
TL;DR: A general synthetic route to conjoint molecules of cephalosporins and aminoglycosides is described, expected that such local delivery of aminglycosides would circumvent the inherent toxicity of am inoglycoside that occurs during systemic exposure within the mammalian host.
Abstract: A general synthetic route to conjoint molecules of cephalosporins and aminoglycosides is described. These molecules were designed as potential substrates for bacterial beta-lactamases, enzymes that hydrolyze the beta-lactam bond of cephalosporins. Hydrolysis of the beta-lactam bond was expected to release the C10-appended aminoglycoside. Since beta-lactamases are sequestered in the periplasmic space of gram-negative bacteria, this sequence of events would liberate aminoglycoside inside such bacteria. It is expected that such local delivery of aminoglycosides would circumvent the inherent toxicity of aminoglycosides that occurs during systemic exposure within the mammalian host.
TL;DR: A receptor profile of several functional in vitro assays for several biogenic amine receptors for the meta'‐iodinated derivative demonstrated high selectivity toward the histamine H3 receptor.
Abstract: Para-substituted aromatic ethers with benzophenone or related structural elements and a 3-(1H-imidazol-4-yl)propyloxy moiety were prepared by Mitsunobu-type ether synthesis or SNAr reaction. Most of the title compounds possess high antagonist potency in histamine H3-receptor assays in vitro as well as in vivo in mouse CNS following oral administration. After defining 4-(3-(1H-imidazol-4-yl)propyloxy)phenyl phenyl methanone as a new lead, structure-activity relationships were investigated for this new class of compounds. Substitution of the meta'-position of the benzophenone moiety with halogen atoms (e.g., iodine, fluorine) led to compounds with high antagonist potency in vitro as well as in vivo (Ki = 9.3 and 4.3 nM, ED50 = 0.7 and 0.47 mg/kg p.o., 18 and 12, respectively). A receptor profile of several functional in vitro assays for several biogenic amine receptors for the meta'-iodinated derivative demonstrated high selectivity toward the histamine H3 receptor.
TL;DR: The 4‐anilinoquinazoline PD 153035 is a potential antitumor agent which acts by inhibiting tyrosine kinase activity of epidermal growth factor receptor (EFGR) via competitive binding at the ATP site of enzyme.
Abstract: The 4-anilinoquinazoline PD 153035 (1) is a potential antitumor agent which acts by inhibiting tyrosine kinase activity of epidermal growth factor receptor (EFGR) via competitive binding at the ATP site of enzyme. A series of cyclic analogues of PD 153035 bearing the 1,4-dioxane ring was prepared by reaction of 6-chloro derivative 5 with several aniline nucleophiles. These were evaluated for their ability to inhibit the EGFR kinase and the growth of primary human tumor cell cultures. All of the new 4-anilinoquinazolines exhibited less potency than PD 153035 against EGFR kinase. However, compounds 2b, 2c, 2e, 2g, and 2h showed higher inhibitory activities than PD 153035 against the growth of A431 tumor cell line. The compound 2b containing 3-chloroaniline ring was as potent as PD 153035 against EGFR kinase and showed about 5.4-fold better potency than PD153035 in the inhibition of growth of A431 cell line with good selectivity.
TL;DR: Compounds 6b and 7d were found to be the most promising compounds among the substances investigated, and were tested for antinociceptive activity by hot plate, tail flick, tail clip, and modified Koster tests.
Abstract: The syntheses of (2-benzothiazolinon-3-yl)propionamide and (2-benzoxazolinon-3-yl)propionamide derivatives are reported. The structures of these compounds are elucidated by their IR and 1H-NMR spectral data, as well as by elemental analysis. The compounds were tested for antinociceptive activity by hot plate, tail flick, tail clip, and modified Koster tests. Compounds 6b and 7d were found to be the most promising compounds among the substances investigated.
TL;DR: Ten polycyclic derivatives related to ellipticine have been synthesised and tested for their intercalating, reverse transcriptase (RT) inhibitory and multidrug resistance efflux pump inhibitory properties, but the MDR efflux Pump inhibitory activities of these derivatives appears to be unrelated to the DNA binding ability.
Abstract: Ten polycyclic derivatives related to ellipticine have been synthesised and tested for their intercalating, reverse transcriptase (RT) inhibitory and multidrug resistance efflux pump inhibitory properties. The intercalating activity and the RT inhibitory activity of the derivatives suggest that ellipticine analogues bind at an allosteric binding site on RT or that this inhibition could be controlled at the DNA level. The MDR efflux pump inhibitory activities of these derivatives, however, appears to be unrelated to the DNA binding ability.
TL;DR: Traditional analytical techniques such as TLC, OR, UV/Vis spectroscopy, and size exclusion chromatography were incapable of providing structural information which would distinguish these NaPPS preparations from each other, and a capillary zone electrophoresis (CZE) method facilitated characterisation of the different NaP PS preparations by a highly reproducible fingerprint.
Abstract: Commercial pentosan polysulfate sodium salts (NaPPS) are highly sulfated polysaccharides derived from beechwood hemicellulose by sulfate esterification with a Mrel range of 1500-6000. The polysaccharide backbone of NaPPS consists of repeating linear units of 1-4 linked beta-D-xylopyranose with laterally substituted 4-methylglucopyranosyluronic acid units glycosidically linked to the 2 position of the main chain at every 10th xylopyranose unit on average. For many years NaPPS has been used for antithrombotic prophylaxis in Europe and interstitial cystitis in the USA and Australia. More recently NaPPS has found veterinary application for the treatment of osteoarthritis and related conditions in domestic animals and is registered for this use in Australia, New Zealand, Canada, UK, Eire, and several Scandanavian countries. At present the use of NaPPS for human disorders is confined to material manufactured by one company. However, for veterinary applications, NaPPS from three manufactures have been described. Since it is well known that the biological activities of sulfated polysaccharides are dependent on their molecular structures we considered it important to characterise these various NaPPS preparations using an established method of analysis. Unfortunately, traditional analytical techniques such as TLC, OR, UV/Vis spectroscopy, and size exclusion chromatography were incapable of providing structural information which would distinguish these NaPPS preparations from each other. In contrast, a capillary zone electrophoresis (CZE) method facilitated characterisation of the different NaPPS by a highly reproducible fingerprint, using a benzene-1,2,4-tricarboxylic acid buffer (8.75 mmol/L, pH = 4.9) with indirect UV detection (lambda = 217 nm) and a special capillary pre-treatment (1 M NaOH for 1 h at 25 degrees C, then running buffer for 120 min at 25 degrees C applying -20 kV). In the present study more than 20 batches of NaPPS from the three manufacturers have been investigated and compared. Minor batch variations were observed to exist for each manufacturer's product however significant differences were detected between NaPPS synthesised by the different manufacturers. Moreover, some preparations showed fingerprint profiles that indicated a more heterogeneous mixture, probably containing other polysaccharides as well.
TL;DR: Compounds containing chlorine and carboxylic substituents are more active and most of the compounds tested showed promising CNS depressant activity comparable with that of standard drug pentobarbitone.
Abstract: The synthesis of some 4-(arylsydnonyl)-2-(4-arylhydrazono-3-methyl-5-oxo-2-pyrazolin-1-yl)- thiazoles by reacting 1-thiocarboxamido-3-methyl-4-(aryihydrazono)-2-pyrazolin-5-ones with different 4-bromoacetyl-3-arylsydnones is described. A few compounds from this series were screened for their anti-inflammatory, analgesic, and CNS depressant activities. Among the tested compounds 6s, 6d, 6n, and 6u showed significant anti-inflammatory activity comparable with that of standard drug Ibuprofen. Compounds containing chlorine and carboxylic substituents are more active. 6f, 6r, and 6u showed marked analgesic activity and most of the compounds tested showed promising CNS depressant activity comparable with that of standard drug pentobarbitone.