Biomedical subjects

M Catto

Publications and source records attributed to M Catto.

9 recordsLinked to original sources

PubMed2001

Coumarins derivatives as dual inhibitors of acetylcholinesterase and monoamine oxidase.

A set of 17 coumarin and 2 chromone derivatives with known inhibitory activity toward monoamine oxidase (MAO) A and B were tested as acetylcholinesterase (AChE) inhibitors. All compounds inhibited AChE with values in the micromolar range (3-100 microM). A kinetic study showed that most compounds acted as noncompetitive AChE inhibitors. This finding may be of interest in the context of Alzheimer's disease because recent observations suggest that MAO and AChE inhibition might decrease beta-amyloid deposition.

Acetylcholinesterase↗

PubMed2000

Inhibition of monoamine oxidases by functionalized coumarin derivatives: biological activities, QSARs, and 3D-QSARs.

A large series of coumarin derivatives (71 compounds) were tested for their monoamine oxidase A and B (MAO-A and MAO-B) inhibitory activity. Most of the compounds acted preferentially on MAO-B with IC(50) values in the micromolar to low-nanomolar range; high inhibitory activities toward MAO-A were also measured for sulfonic acid esters. The most active compound was 7-[(3, 4-difluorobenzyl)oxy]-3,4-dimethylcoumarin, with an IC(50) value toward MAO-B of 1.14 nM. A QSAR study of 7-X-benzyloxy meta-substituted 3,4-dimethylcoumarin derivatives acting on MAO-B yielded good statistical results (q(2)() = 0.72, r(2)() = 0.86), revealing the importance of lipophilic interactions in modulating the inhibition and excluding any dependence on electronic properties. CoMFA was performed on two data sets of MAO-A and MAO-B inhibitors. The GOLPE procedure, with variable selection criteria, was applied to improve the predictivity of the models and to facilitate the graphical interpretation of results.

Animals↗

PubMed1998

Inhibition of monoamine oxidase-B by condensed pyridazines and pyrimidines: effects of lipophilicity and structure-activity relationships.

A number of condensed pyridazines and pyrimidines were synthesized and tested for their monoamine oxidase-A (MAO-A) and MAO-B inhibitory activity. Their lipophilicity was examined by measuring partition coefficients and RP-HPLC capacity factors, revealing some peculiar electronic and conformational effects. Further insights were obtained by X-ray crystallography and a thermodynamic study of RP-HPLC retention. Structure-activity relations highlighted the main factors determining both selectivity and inhibitory potency. Thus, while most of the condensed pyridazines were reversible inhibitors of MAO-B with little or no MAO-A effects, the pyrimidine derivatives proved to be reversible and selective MAO-A inhibitors. Substituents on the diazine nucleus modulated enzyme inhibition. A QSAR analysis of X-substituted 3-X-phenyl-5H-indeno[1,2-c]pyridazin-5-ones showed lipophilicity to increase MAO-B and not MAO-A inhibitory activity.

Animals↗

PubMed1977

The significance of bone islands, cystic areas and sclerotic areas in dysbaric osteonecrosis.

Dysbaric osteonecrosis is a major hazard to compressed air workers and an increasing hazard to divers. Symptomless osteonecrosis is best recognised by radiology and it is of fundamental importance that interpretation be reliable and accurate. There is much controversy concerning the significance of bone islands and cystic areas; several authors report bone islands and cystic areas to be up to eight times more frequent in compressed air workers and divers and believe that these represent positive evidence of osteonecrosis. Skeletal radiographs of 100 Royal Navy divers, all of whom were at risk to osteonecrosis were matched for age and rank with 100 controls, none of whom had been exposed to high pressures. The radiographs were interpreted by three radiologists working independently without knowing whether the radiographs were in the diving or control group. It is concluded that bone islands, cystic areas and sclerotic areas, as described in this text, occur with equal frequency in divers as in the normal population and do not represent positive evidence of osteonecrosis. The report includes autopsy studies of the proximal femur and proximal humerus in six diving fatalities. Five bone islands in the proximal humerus and one in the femoral neck were studied in bones removed from five divers. In the sixth case a cyst was seen to develop radiologically in the femoral neck and then reduce in size over 3 years and 10 months. Slab radiographs and histological section in all cases show no evidence of osteonecrosis.

Adult↗

PubMed1977