Il Farmaco; edizione scientifica最新文献

In this paper the photochemical and photobiological properties of 8,8-desmethyl-xanthyletine (homopsoralen) have been studied. This drug forms a molecular complex with DNA undergoing intercalation between two base pairs of the macromolecule. By subsequent irradiation (365 nm) the compound photobinds covalently to the macromolecule showing an initial DNA-photobinding rate higher than that of 8-methoxypsoralen. In the photoreaction with DNA the drug effectively forms inter-strand cross-linkages. Its ability to generate singlet oxygen when irradiated with ultraviolet light is markedly higher than that of 8-MOP. Homopsoralen when irradiated in water solution undergoes effective photolysis. The drug shows a lower antiproliferative activity on diploid yeast (D 7) than 8-MOP and an almost parallel mutagenic activity. Also the gene convertogenic activity, determined on the same yeast strain, is lower than that of 8-MOP. Homopsoralen does not show any skin phototoxicity on guinea-pig skin. Taking into account its DNA-photobinding capacity, its antiproliferative activity, its reduced genotoxicity and lack of skin-phototoxicity homopsoralen may deserve further studies for evaluating its photochemotherapeutic activity.

Two series of experiments were performed on rat chronic ulcer in order to assess the possible curative and mucosal protective properties of 2 week treatments, or the preventive properties of 4 week treatments with antisecretory agents, acting with different mechanisms of action. At the end of the treatments the gastric secretory and motor responsiveness to a gastrin-like stimulus was simultaneously evaluated. The results support the view that antimuscarinic agents as well as H2-blockers cannot be defined as protective and that after a 4 week treatment they can induce modifications of gastric functions.

As a part of a study on analgesic and antiinflammatory active condensed heterocyclic compounds containing the pyrimidinic ring, a number of 6H-1,3,4-thiadiazolo [3',2':1,2]-5-oxopyrimido [5,4-b]indole and 1-phenyl-6H-1,2,4-triazolo [1',5':1,2]-5-oxopyrimido [5,4-b] indole were synthesized and tested. The results of pharmacological assays are reported and discussed.

A new series of 5-(4-halobenzoyl)-4-amino-3-(2-dialkylamino-ethylthio)thieno [2,3-c] and [3,2-d] isothiazole derivatives has been synthetized. The compounds were evaluated for antifungal activity on yeast and dermatophytes. The compound (VI b) resulted about thirty times less potent than miconazole on dermatophytes.

The characterization of mono- and dimethylated 5-substituted uracils was re-examined. Analysis of their physicochemical properties (pKa, U.V., delta 1H-N.M.R.) affords insight into the structural characteristics of 5-substituted uracil alkylated at the ring nitrogens.

The central effects of carboxyethyl-gamma-aminobutyric acid (CEGABA) have been studied both in rabbits and in the guinea pig myoclonus model. This drug caused EEG synchronization and behavioural sedation both after intravenous (i.v.) and intracerebroventricular (i.c.v.) administration in a dose-dependent manner, in rabbits. CEGABA showed a protective action against myoclonus induced by means of L-5-HTP in young guinea pigs. These data substantiate the hypothesis that CEGABA is a drug active on the central nervous system and probably exerts its action by strengthening cortical inhibition and/or directly acting on lower brainstem.

Khellin, a naturally occurring furochromone, used in the past as a coronary vasodilator, has recently been used in the photochemotherapeutic treatment of vitiligo and psoriasis. With the aim of elucidating its mechanism of action, the interactions both in ground and excited states between the drug and DNA were studied in vitro. Khellin forms in the dark a molecular complex with DNA. By subsequent irradiation (365 nm) the drug photoconjugates covalently with the macromolecule, although the rate of photobinding is rather low. The in vivo photobinding of khellin to the DNA of Ehrlich ascites tumor cells is also low. In photoaddition with the macromolecule the drug forms inter-strand cross-links, although again in small amounts. The furan side monoadduct between khellin and thymine, formed in the photoreaction between the drug and DNA, was isolated and characterized, and shows a cis-syn configuration.

A series of 2-(2'-acylhydrazino)-3-ethoxycarbonyl-3-aryl (or alkyl)-pyrrole derivatives was synthesized and submitted to in vitro microbiological screening. Most derivatives showed considerable antibacterial and antifungal activities.

This report describes the effects of a fungal polysaccharide mixture on the Experimental Allergic Encephalitis (EAE) in guinea pigs. The clinical, histopathological and IgG intrathecal synthesis related studies in the EAE sensitized group was compared with that observed in EAE sensitized groups treated with fungal polysaccharides. The results indicate that the fungal polysaccharide mixture is capable of inducing a more localized and milder inflammatory reaction in the guinea pig with EAE. We hypothesize that the fungal polysaccharides can activate complement by the alternative pathway, subtracting it to the specific immune response to EAE.

The 1,1' disulfones obtained by oxidation of the corresponding dl and meso 3,3'(1,2-ethanediyl)bis [2-aryl-4-thiazolidinone] compounds previously investigated, were evaluated as anti-histamine, anti-inflammatory, analgesic and anti-pyretic agents. All 2,2' fluorophenyl compounds were found to be significantly active in inhibiting carrageenin-induced edema, whereas only para-substituted derivatives were active on the histamine-induced bronchospasm in the guinea-pig. They also showed analgesic effects that reached and sometimes exceeded those of indomethacin and phenylbutazone used as reference drugs.