Monica Malagoli

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.

'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.

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.