Rosaria Bossa

Synthesis and cardiotonic activity of 2-indolinones

Abstract The paper reports the synthesis of 3-(2,5-dimethoxybenzylidene)- 2 and 3-(4-pyridylmethylene)-2-indolinones 3 which, as expected, proved to have significant positive inotropic activity. On the contrary, 3-(2,5-dimethoxybenzyl)- 4 and 3-(4-pyridylmethyl)-2-indolinones 5 , obtained by reduction of the corresponding compounds 2 and 3 , were devoid of cardiotonic activity.

Synthesis and cardiotonic activity of imidazo[2,l-b]thiazoles bearing a lactam ring

Summary This paper describes the synthesis of 6-substituted imidazo[2,1- b ]thiazoles with a lactam ring connected, by means of a methine group, to the 5-position. The pharmacological results show that interesting cardiotonic activity is obtained when the lactam ring is pseudothiohydantoin ( 8 ) or barbituric acid ( 9 ). Even the substituent at position 6 plays an important role in the pharmacological behavior of these derivatives. The following activity rank order was observed: phenyl > methyl > chlorine.

Synthesis and potential coanthracyclinic activity of substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones†

Summary A compound endowed with coanthracyclinic activity should potentiate the antitumor activity of anthracyclines while counteracting their cardiodepressant effect. We now report the synthesis and configuration of a series of substituted 3-(5-imidazo[2,1- b ]thiazolylmethylene)-2-indolinones which were tested for both cardiotonic and cytotoxic activity. Several compounds were potent cytotoxic agents and two of them (in particular 3-[6-(2,5-dimethoxyphenyl)-5-imidazo[2,1- b ]thiazolylmethylene]-2 -indolinone, which showed even cardiotonic activity, are potential coanthracyclinic agents.

Synthesis and cardiotonic activity of pyridylmethylene-2-indolinones

Abstract The title compounds were prepared by reaction of 3 2-indolinones with 3 different pyridinecarboxaldehydes. In one case ( 7b ) it was possible to isolate and characterize both the E and Z isomers. In the other cases (except 5b ) the E isomer was largely predominant or the only one present. The pharmacological activity of E- 7b was not significantly different from that of Z- 7b . Compound 6b , arising from the reaction of 5-methoxy-2-indolinone with 3-pyridinecarboxaldehyde, was significantly more active than the other compounds prepared.

Potential anti-tumor agents XVI. Imidazo[2,1-b]thiazoles

Abstract A number of imidazo[2,1-b]thiazoles have been synthesized and tested in mice bearing Ehrlich ascites tumor cells. The nitrogen mustard 5 had a T C of 140 at 8 mg/kg.

Synthesis and cardiotonic activity of aryl- or pyridyl-substituted fused imidazoles

Abstract The syntheses of 4 different fused imidazoles bearing a 2,5-dimethoxyphenyl group or a pyridyl group are reported. All the heterocycles, except 2a , display positive inotropic activity. Some are approximately equipotent with sulmazole, and the imidazo[2,1- b ]benzothiazole that bears a 4-pyridyl group is the most active of whole series.

Potential antitumor agents. XX: (1) 6-Anilinoimidazo[2,1-b]thiazoles

The synthesis of 6-anilinoimidazo[2,1-b]thiazoles, related to the well-known antitumor agent amsacrine, is reported. The cytotoxic activity of the new compounds was evaluated on HeLa cells. Compound 3a, the most closely related to amsacrine, was significantly active.

Dihydropyridines bearing an imidazo[2,1-b]thiazole system

Summary This paper reports the synthesis of imidazo[2,1- b ]thiazoles, bearing a dihydropyridine ring at the 5 or 6 position, which were tested for antiarrhythmic, inotropic and chronotropic activities. Nine of the ten compounds bearing double bond at the 2,3 position and the same dihydropyridine as nifedipine at the 5 position, were antiarrhythmic; moreover one of them (bearing a methyl group at the 2 position) was devoid of negative inotropic activity.

Effect of various anti-tumor drugs on energetic processes

Abstract Activity of some anti-tumor drugs on respiration and anaerobic glycolysis of Ehrlichs ascites cells and of rat brain homogenates, as well as on respiration of rat liver homogenates as investigated. Cycle-specific drugs, as Bleomycin, Cytosine arabinoside and Hydroxyurea, are inactive on all tissues examined. Peptichemio and BCNU, cycle-aspecific drugs, inhibit respiration and anaerobic glycolysis of tumor cells. VM 26, Daunomycin and Adriamycin are ineffective on anaerobic glycolysis of tumor cells; VM 26 inhibits respiration, whereas Daunomycin at low concentrations and Adriamycin have a stimulating effect.

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.