Biomedical subjects
Publications and source records attributed to M Di Bella.
The antitumor activity of the methyl-6-chloro-4H-1,2,4-benzothiadiazin-3-yl-S-carbamothioate+ ++-S,S,-dioxide (1) and the methyl-4H-1,2,4-benzothiadiazin-3-yl-carbamodithioate-S,S-di oxide (2), has been evaluated. Compound 2 passed activity criteria for leukemia P388 and was also moderately active against transplanted mouse tumor L1210 leukemia and M5076 sarcoma.
A series of N-arylglycine derivatives and their thioisosters (1-10) was synthesized and evaluated as in vitro aldose reductase inhibitors. Among these, (6-chloro-1,2,4-benzothiadiazine-1,1-dioxide-3-yl)-2-propanoic acid (5) shows an inhibitory activity (IC50:5.1 microM) comparable to Alrestatin.
A series of carbamimidothioic acid phenylmethyl ester salts and their N,N'-tetramethyl derivatives were synthesized, many of which exert an interesting inhibiting action on Gram-positive and Gram-negative bacteria and also on fungi. This activity is noteworthy in view of the large number of strains antagonized; the (3,4,5-trichlorophenyl) methyl ester chloride of carbamimidothioic acid appeared to be the best term of the series. The possible influence on this activity of decomposition kinetics to the corresponding mercapto-derivatives was investigated and compared with that of a series of N,N'-tetramethyl derivatives of previously studied carbamimidothioic acid phenyl ester salts.
In this study we tested the potential taurine-antagonistic properties of three rigid analogs of taurine, 3-amino- (1), 3-hydrazino- (2) and 3-aminomethyl-1,2,4-benzothiadiazine-1,1-dioxide (3), which were prepared in our laboratory, using TAG (6-aminomethyl-3-methyl-1,2,4-benzothiadiazine-1,1- dioxide) (4), the only antagonist of taurine so far available, as reference compound in "in vivo" and "in vitro" experiments. Some physicochemical properties of (1), (2) and (3) were studied and the synthesis of TAG (4) was improved with a new preparative method. A dose-effect study performed by injecting intracerebroventricularly (1), (2) and (3) showed that these compounds have none of exciting effects exerted by the high doses of TAG (4). (1) and (3) as well as TAG (4), were found to antagonize the controlateral turning induced by the intracerebro injection of taurine and to potentiate the sedative effect of diazepam. We failed to find specific binding for taurine in different brain synaptic membrane preparations using 3H-taurine as radioligand and taurine, (1) and (3) as binding displacer. (1), (3) and TAG (4) however were found to antagonize the inhibitory effect of taurine on 3H-diazepam binding. These results seem to indicative that at least (1) and (3), which were more extensively studied than (2) because of their better solubility, are taurine antagonists with an apparent better selectivity than TAG (4).
The scavenging activity of some isosteric antiinflammatory heteoarylalkanoic acids with respect to oxygen-free radicals has been studied. All the compounds were found to inhibit the depolymerization of hyaluronic acid due to enzymatically or chemically generated hydroxyl radicals. The reduced consumption of oxygen by xanthine oxidase indicates a cotemporaneous phenomenon of enzymatic inhibition.
The 1-octanol/water partition coefficients of a series of antimicrobial S-aryl(tetramethyl)isothiouronium salts, were determined. The concentration of the solute in the two phases was measured by means of HPLC. The values of the hydrophobic parameters thus obtained were correlated to the corresponding capacity factors (log Kw) and compared with those expected on the basis of additive-constitutive principles. The deviations were interpreted quantitatively on the basis of electronic interactions of the substituents in the benzene ring. Equations correlating structural features and antimicrobial activity of some studied compounds by means of molecular parameters were formulated.
A series of 3-(4H-1,2,4-benzothiadiazine-1,1-dioxide-3-yl-thio)-propanoic acids was synthesized in order to study their possible antiinflammatory in comparison with the corresponding lower homologues and isosters previously studied. Most of the compounds proved effective against carrageenan-induced plantar oedema. The possible influence of some chemico-physical parameters on the occurrence of this biological activity was investigated.
The interaction of some isosteric and homologues series of antiiflammatory heteroarylalkanoic acids with human serum albumin (HSA) was investigated by UV difference spectroscopy and fluorescence quenching. All tested compounds were shown to bind to HSA. The interaction with surfactants and the linear relationship between binding constants and pKa suggest that electrostatic force is dominant in the binding of these compounds and that the binding site consists of a cationic charge near an hydrophobic surface.
A series of 3-(4H-1,2,4-benzothiadiazine-1,1-dioxide-3-ylamino)-propanoic acids was synthesized in order to study their possible antiinflammatory activity and to compare it with the corresponding homologous or isoster series previously studied. Of particular interest is parent compound 1, which is unsubstituted in the benzenoid moiety and exerts a very marked inhibitory effect on carrageenan-induced plantar oedema greater than that observed for any of the terms of the other series hitherto studied. The possible influence of some chemico-physical parameters on the occurrence of this antiinflammatory activity is investigated.
Explore the source record for details and available documents.
A series of S-Aryl(tetramethyl)isothiouronium salts were prepared and evaluated in vitro for antimicrobial activity. Some compounds revealed interesting inhibiting action on Gram-positive bacteria which is noteworthy in view of the large number of strains antagonized and of the low MIC values. The possible influence of decomposition kinetics to the corresponding mercaptoderivatives was intestigated and compared with those of salts previously studied.
A series of dialkylamino, pyrrolidyl and morpholyl-alkyl-derivatives of 3-amino-1,2,4-benzothiadiazine-1,1-dioxide, 7- or 5,7-halogen substituted in the benzenoid moiety, was prepared and their cardiovascular activity studied. Most of the substances in question were capable of inducing a significant decrease in mean arterial blood pressure; some of them tended to increase pulse pressure or to cause bradycardia, an effect which was noted particularly in the case of compound 10 which reduced heart-rate by 85%. The structure/activity relationship of these substances, of the 6- and 6,7-halogen substituted isomers and of their corresponding non-substituted progenitors is examined.
Cigarette smoking, hypercholesterolaemia, hypertriglyceridaemia, are all known risk factors for atherosclerotic vascular lesions. Often they are associated with alterations mainly due to increased haematocrit (smoking) or to the influence of triglycerides and cholesterol on the erythrocyte membrane or plasma viscosity. In order to eliminate these factors, washed red blood cells, poor in leucocytes and platelets, in a suspension with phosphate saline buffer were studied. 20 heavy smokers, 40 patients with hyperlipidaemia (26 II a or b; 14 IV) and 50 healthy people were considered. Red blood cell viscosity was calculated at 4 shear rate between 0.37 and 69.5 sec-1. Red blood cell deformability, as an indicator of cell filtration through Nucleopore membranes was also studied. There was no difference in the filtration index among the subjects under study. Red blood cell viscosity increased in smokers and in patients with hyperlipidaemia.
Risk factors for atherosclerosis are often associated with haemorheological changes. On this point, obesity (recently advocated as an independent risk factor) was not much studied and with not univocal results. We have studied 70 obese patients (BMI greater than 30) and 50 healthy subjects (BMI less than 25). Among obese 26 had no more pathologies, 29 had hypertension, 3 suffered from ischemic heart disease, 3 suffered from occlusive arteriopathy, 9 were hyperlipidemic, 10 were smokers. We determined plasma viscosity and whole blood viscosity (at haematocrit corrected to 45% too). Washed erythrocytes, poor in leucocytes and platelets and resuspended in phosphate-buffered saline, were used for study of erythrocyte viscosity and deformability. Obese patients showed raised mean blood viscosity values when compared to healthy controls (p less than 0.01); an even more significant increase (p less than 0.001) was found concerning plasma viscosity and fibrinogen. Erythrocyte viscosity and red blood cell filterability index did not show any significant difference. We found no significant correlation between viscosity values and presence of hypertension, hyperlipidemia and smoking habit among obese. In conclusion, the higher vasculopathy incidence might be caused by an increase in blood viscosity, mostly due to plasmatic component. This fact appears to be independent from the presence of atherosclerosis complications or other risk factors.
Peripheral atherosclerotic arteriopathies are characterised by increased blood viscosity and, according to some, by a reduction in red blood cell deformability. Red blood cell viscosity was studied in 40 atherosclerosic patients (14 carotid and 26 aortoiliacofemoral lesions). All patients were subjected to the standard diagnostic examination (Doppler velocimetry, etc.). Fifty healthy non-smokers of the same sex and 20 heavy smokers were studied as controls. The viscosity of the whole blood, and plasma and blood fibrinogen were assayed. In studying erythrocyte viscosity, cells poor in leucocytes and platelets suspended in a saline phosphate buffer were employed. The atherosclerotic patients presented significantly higher mean levels of erythrocyte viscosity (p less than 0.01) and the increase in plasma viscosity and blood fibrinogen was also statistically significant. The viscosity of the whole blood was also increased in these patients (p less than 0.001). The increase in blood viscosity in subjects with peripheral arteriopathies therefore appears to be attributable to the plasma and to rheological alterations in the red blood cells.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.