Effects of tiaprofenic acid on urinary pyridinium crosslinks in adjuvant arthritic rats: Comparison with doxycycline

Weithmann, K. U.; Schlotte, V.; Jeske, V.; Seiffge, D.; Laber, A.; Haase, Burkhard; Schleyerbach, R

doi:10.1007/s000110050182

Cited by 7 publications

(2 citation statements)

References 30 publications

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“…The catalytic domain of human recombinant MMP-8 (hMMP-8cd; Gly99-Gln271; MW 19.9 kDa) was obtained as described previously. 26 Biological activities were determined in 96-well titer plate format in a luminescence spectrometer (LS 50B, Perkin-Elmer, Langen, FRG) using the quenched fluorigenic substrate 27 7-methoxycoumarin-4-yl acetyl-Pro-Leu-Gly-Leu-3-(2′,4′-dinitrophenyl)-L-2,3-diaminopropionyl-Ala-Arg-NH2 (λex ) 328 nm, λem ) 393 nm; available from Bachem, Heidelberg, Germany). Each well contained 70 µL of buffer (0.1 mol/L Tris/ HCl, pH 7.5; 0.1 mol/L NaCl; 0.01 mol/L CaCl2; 0.05% Brij 35), 10 µL of enzyme, and 10 µL of drug in 10% DMSO.…”

Section: Methodsmentioning

confidence: 99%

Quantitative Structure−Activity Relationship of Human Neutrophil Collagenase (MMP-8) Inhibitors Using Comparative Molecular Field Analysis and X-ray Structure Analysis

Matter¹,

Schwab²,

Barbier³

et al. 1999

J. Med. Chem.

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A set of 90 novel 2-(arylsulfonyl)-1,2,3, 4-tetrahydroisoquinoline-3-carboxylates and -hydroxamates as inhibitors of the matrix metalloproteinase human neutrophil collagenase (MMP-8) was designed, synthesized, and investigated by 3D-QSAR techniques (CoMFA, CoMSIA) and X-ray structure analysis. Docking studies of a reference compound are based on crystal structures of MMP-8 complexed with peptidic inhibitors to propose a model of its bioactive conformation. This model was validated by a 1. 7 A X-ray structure of the catalytic domain of MMP-8. The 3D-QSAR models based on a superposition rule derived from these docking studies were validated using conventional and cross-validated r2 values using the leave-one-out method, repeated analyses using two randomly chosen cross-validation groups plus randomization of biological activities. This led to consistent and highly predictive 3D-QSAR models with good correlation coefficients for both CoMFA and CoMSIA, which were found to correspond to experimentally determined MMP-8 catalytic site topology in terms of steric, electrostatic, and hydrophobic complementarity. Subsets selected as smaller training sets using 2D fingerprints and maximum dissimilarity methods resulted in 3D-QSAR models with remarkable correlation coefficients and a high predictive power. This allowed to compensate the weaker zinc binding properties of carboxylates by introducing optimal fitting P1' residues. The final QSAR information agrees with all experimental data for the binding topology and thus provides clear guidelines and accurate activity predictions for novel MMP-8 inhibitors.

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Section: Methodsmentioning

confidence: 99%

Quantitative Structure−Activity Relationship of Human Neutrophil Collagenase (MMP-8) Inhibitors Using Comparative Molecular Field Analysis and X-ray Structure Analysis

Matter¹,

Schwab²,

Barbier³

et al. 1999

J. Med. Chem.

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“…CIA was induced by a footpad method because CII plus adjuvant injection into the base of the tail causes weaker effects as compared to a direct injection into the paw [29]; this was confirmed also in our laboratory. In the latest studies of other investigators, this method is widely used for CIA induction [18,30].…”

Section: Discussionmentioning

confidence: 85%

Kolagenu sukeltas Wistar ir Lewis žiurkių artritas ir (Pro-)antioksidantinės sistemos būklė

Leonavičienė¹,

Bradūnaitė²,

Vaitkienė³

et al. 2008

Biologija

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The aim of this study was to investigate the development of collagen-induced arthritis (CIA) in male and female Wistar and Lewis rats and establish relationships between clinical status and the levels of serum oxidative products. CIA was induced in 64 rats divided randomly into three groups. Animals of the 1st group received one 0.1 ml injection of bovine type II collagen (CII, in dose of 0.1 mg/rat) emulsified in incomplete Freund's adjuvant (IFA). Rats of the 2nd group were immunized twice: on day 0 (dose of CII 0.1 mg/rat) and day 7 (dose of CII 0.05 mg/rat), and the animals of the 3rd group received one 0.1 ml injection of emulsion consisting of CII (0.1 mg/rat) in IFA and muramyldipeptide (MDP, in dose of 3 mg/ml). Serum oxidative products such as malondialdehyde (MDA), anti-oxidative enzyme catalase (CAT), total antioxidant activity (AOA), and arthritic profiles based on paw swelling, development of polyarthritis and histological changes in joints were measured in rats with CIA. Our findings have demonstrated that CIA develops in both sexes of Wistar and Lewis rats and the disease that occurs is an inflammatory erosive arthritis. Examination of the clinical course of the disease and the subsequent histological analysis disclosed a slight less aggressive disease in Wistar than in Lewis rats and in female than in male animals. The most severe arthritis developed in the 3rd group of male Lewis rats. CIA induced significant changes in the parameters of the pro-/antioxidant status of serum. Comparison of the oxidative statuses of both strains of rats with CIA and those of healthy animals revealed more elevated MDA levels in the serum of Wistar than Lewis rats. More evidently in the serum of these rats the level of total AOA was reduced, especially in the 3rd group of animals. More susceptible to CIA, Lewis rats showed a lower MDA production as compared with Wistar animals, and the lowest CAT activity in the serum of these rats was observed. In conclusion, attenuated inflammatory response and pathomorphological changes in joints were more observed in female animals of both strains. Male Lewis rats were most susceptible to CIA. On the basis of increased lipid peroxidation and decreased levels of AOA and enzyme CAT activity, CIA rats are subject to oxidative stress.

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Safety Pharmacology of Drugs with Osteoarthritis-Related Activity

Raiss¹

2006

Drug Discovery and Evaluation

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Effects of tiaprofenic acid on urinary pyridinium crosslinks in adjuvant arthritic rats: Comparison with doxycycline

Cited by 7 publications

References 30 publications

Quantitative Structure−Activity Relationship of Human Neutrophil Collagenase (MMP-8) Inhibitors Using Comparative Molecular Field Analysis and X-ray Structure Analysis

Quantitative Structure−Activity Relationship of Human Neutrophil Collagenase (MMP-8) Inhibitors Using Comparative Molecular Field Analysis and X-ray Structure Analysis

Kolagenu sukeltas Wistar ir Lewis žiurkių artritas ir (Pro-)antioksidantinės sistemos būklė

Safety Pharmacology of Drugs with Osteoarthritis-Related Activity

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