Mario Castelli

Synthesis and antiproliferative activity of some benzimidazole-4,7-dione derivatives.

A series of benzimidazole-4,7-diones bearing at the 2-position the thiomethyl group or the 2-pyridyl moiety has been synthesized and tested in vitro on three tumor cell lines. Two of them show a very good antiproliferative effect. Compounds 1 and 2d are more active or equiactive, respectively, than MMC against human lymphoblastic leukemia. Both compounds exhibit high activity on human non-Hodgkin lymphoma. Compound 1 is non toxic at all the concentrations used in the antiproliferative assay and 2d is toxic only at high concentration.

Characterization of the contractile activity of dopamine on the rat isolated seminal vesicle.

The mechanism of the contractile effect of dopamine (DA) on the rat isolated seminal vesicle was studied. Cocaine (10 microM/1 in the organ bath, 30 min before DA) and 6-OHDA (50 mg/kg i.v. 24 hr before removal of the seminal vesicle) almost completely prevented the contractile effect of DA. Drugs known to have an affinity for DA receptors or for alpha-adrenoceptors antagonized the contractile effect of DA, the rank order of potency being: prazosin greater than phentolamine greater than yohimbine greater than clonidine greater than sulpiride greater than apomorphine greater than haloperidol. The antagonism was in each case greater against DA than against noradrenaline (NA), used for comparison; selectivity for DA being highest in the case of prazosin and sulpiride. Taken together, these findings indicate that DA makes the rat seminal vesicle contract mostly by means of an indirect mechanism, binding presynaptic DA-receptors and, in part, presynaptic alpha-adrenoceptors as well; or, alternatively, binding presynaptic DA-receptors which have some links with alpha 2-adrenoceptors; the consequence being in either case the release of NA from sympathetic nerve endings.

'In vitro' study of chemotherapeutic activity of sulphimidazole on some sensitive and metronidazole-resistant Trichomonas vaginalis strains.

Trichomonacidal treatment based on 5-nitroimidazoles is problematic both when Metronidazole, the drug of choice, is ineffective owing to the presence of resistant strains and when bacterial aerobic infections are present. Sulphimidazole (SIZ) possesses two distinct functional groups: one sulphonamide, the other 5-nitroimidazole. Since SIZ is active against aerobic and anaerobic bacteria, we set out to discover whether, in view of the presence of the 5-nitroimidazole group, it could also be effective against Trichomonas vaginalis. Twelve strains of T. vaginalis were cultured in Modified Thioglycate Medium in anaerobic conditions; subsequently, their growth was monitored in the presence of Metronidazole (MZ), SIZ, Sulphamethoxazole (SMX), Trimethoprim (TMP) and their associations. Eight strains proved to be sensitive to Metronidazole (minimum lethal concentration=0.5 microgml(-1)) and four to be resistant (minimum lethal concentration=40-60 microgml(-1)). SIZ was active against both the sensitive and the Metronidazole-resistant strains (minimum lethal concentrations=0.5-1 and 10 microgml(-1), respectively), thus showing that the chemotherapeutic activities of the two functional groups coexisting in SIZ remain unimpaired.

Synthesis and antiproliferative activity of 3-substituted 1H-indole [3,2-d]-1,2,3-triazin-4 (3H)-ones

Some 3-substituted indole-triazin-4-ones were synthesized. Their antiproliferative activity against chronic myeloid leukaemia and non-Hodgkin lymphoma human cells was compared in vitro with that of daunorubicin. One compound appeared to be very effective against human CML.

Effect of glycyrrhizin and its diastereoisomers on the growth of human tumour cells: preliminary findings

It is known that some pentacyclic triterpenoids present in nature possess anti‐tumour activity. In a recent study we demonstrated that a prolonged glycyrrhizin treatment was effective in modifying the survival pattern of mice with Ehrlich ascites tumour. Moreover, it has been demonstrated that 18α‐glycyrrhetinic acid, 18β‐glycyrrhetinic acid and glycyrrhizin effectively inhibited the inception and growth of skin tumour. In an in vitro study these drugs also proved effective against the growth and differentiation of mouse melanoma cells. In this work we investigated the effect of 18α‐glycyrrhetinic acid, 18β‐glycyrrhetinic acid and glycyrrhizin on the growth of human tumour cells: two lymphomas and two leukaemias. The results were compared with those afforded by equimolecular doses of daunorubicin and showed that all three substances were fairly active, particulary against leukaemia cells.

Griseofulvin-methisoprinol combination in the treatment of herpes zoster

A total of 57 herpes zoster patients (28 men and 28 women) were randomly assigned to one of the following four treatments: griseofulvin, 125 mg four times daily; methisoprinol, 1 g four times daily; griseofulvin plus methisoprinol (dosage schedules as above); placebo, four times daily. Griseofulvin had no effect at all, methisoprinol both significantly accelerated drying of vesicles and reduced pain, and the combination of griseofulvin and methisoprinol turned out to be significantly more effective in reducing pain than methisoprinol alone. The present results suggest a new effective treatment for herpes zoster disease.

In vitro Activity of Trimethoprim in Association with Sulfimidazole against Aerobic Gram-Negative and Gram-Positive Microorganisms and Clostridia

The in vitro activity of a chemotherapeutic agent, sulfimidazole (SIZ), obtained by combining two molecules belonging to groups of extremely different antibacterial drugs, p-aminobenzene sulfonamide and a derivative with a 5-nitroimidazole ring, was studied. In association with trimethoprim, SIZ induces an intense synergistic antibacterial effect on gram-negative and gram-positive aerobic microorganisms and Clostridia. The results show that, in SIZ, the activity of each starting molecule remains unchanged providing that its structure-action relationship is kept intact.

In vitro activity of sulphimidazole alone and in association with trimethoprim against enteric pathogens

Sulphimidazole is a new sulphonamide belonging to the class of intestinal sulphonamides and characterized by the fact that it is active even in vitro. It has the heterocyclic ring of 5-nitroimidazoles on amidic nitrogen. Its antibacterial activity is similar to that of the classical sulphonamides but differs in that it also combats certain anaerobic bacteria such as Clostridium botulinum. This effect is completely absent in the case of sulphadiazine and sulphamethoxazole. Also, since p-amino-benzene-sulphonamide is present in the molecule, the drug acts in synergism with trimethoprim against certain aerobic or facultative strains of enteric pathogens.

Bactericidal and antineoplastic effect of combination of norfloxacin and adriamycin

Norfloxacin and adriamycin were tested alone and in combination for bactericidal activity against different strains of gram-negative bacteria. The antitumoral effect of a combination of norfloxacin and adriamycin was determined in mice bearing Ehrlich ascites carcinoma and in mice bearing P 388 leukemia. No interference with the antibacterial activity of norfloxacin or with the antitumoral activity of adriamycin was observed.

Metronidazole-quinolone combination: Antibacterial activity in vitro

Combination of metronidazole and oxolinic or pipemidic acid were tested in vitro against some of the bacteria most commonly responsible for genito-urinary infections (E. coli, K. pneumoniae, Enterob. cloacae, Serratia marcescens, Pr. mirabilis, Pr. morganii, Str. faecalis and 3 strains of Ps. aeruginosa). The metronidazole-oxolinic acid combination was found to be additive or synergistic against E. coli, K. pneumoniae, Enterob. cloacae and Serratia marcescens. The results show that subinhibitory concentrations of oxolinic acid may reveal an activity of metronidazole against aerobic and facultative anaerobic bacteria, under aerobic conditions.