Rita Morigi

Synthesis and antitubercular activity of imidazo[2,1-b]thiazoles

A number of selected imidazo[2,1-b]thiazoles entered the screening at the Tuberculosis Antimicrobial Acquisition and Coordinating Facility (TAACF) and one of these compounds, 2-chloro-6-phenylimidazo[2,1-b]thiazole, showed antitubercular activity. On this basis we planned the synthesis of new analogues bearing a substituted ring at the 6 position. For one compound only (2-chloro-6-p-chlorophenylimidazo[2,1-b]thiazole) the 5-nitroso derivative was also prepared. The antitubercular activity of these compounds was compared with the known analogues lacking the chlorine at the 2 position. 5-Nitroso-6-p-chlorophenylimidazo[2,1-b]thiazole showed potent antitubercular activity.

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.

4-Aminopyridine derivatives with antiamnesic activity

Acetylcholine (Ach) enhancement, useful in the treatment of Alzheimers disease (AD), may be obtained by means of ion channel modulators such as 4-aminopyridine (4-AP). 4-AP is also the central ring of tacrine, the first drug approved for the treatment of AD. The synthesis and pharmacological activity of three 4-AP derivatives, prepared with the aim of improving their antiamnesic activity, is here described. In two of these compounds 4-AP is connected to 4-aminobutyric acid (GABA), whereas in the third it is connected to 2-indolinone, i.e., the skeleton of linopirdine, another Ach enhancing agent. The new compounds showed potent antiamnesic activity in comparison with piracetam.

6-Thienyl and 6-phenylimidazo[2,1-b]thiazoles as inhibitors of mitochondrial NADH dehydrogenase

Starting from the potent inhibitory effect of the previously described 2-methyl-6-(2-thienyl)imidazo[2,1-b]thiazole on mitochondrial complex I, we prepared a series of derivatives in order to study the effect of a different substitution at the positions 2, 5 and 6. The replacement of the thienyl group at position 6 with a phenyl group does not modify the biological behaviour of the lead compound, whereas the shift of the methyl group from position 2 to position 5 yields a compound devoid of inhibitory effects. In both the 6-thienyl and 6-phenyl series, the lengthening of the chain at position 2 has provided useful information to outline the structural determinants of the ubiquinone antagonist action in imidazothiazole derivatives.

Synthesis and potential coanthracyclinic activity of pyridylmethylene and indolylmethylene lactams

The synthesis of pyridylmethylene lactams and indolylmethylene-2-indolinones is reported. These compounds were tested for their cytotoxic and positive inotropic activity. The presence of both the effects (coanthracyclinic activity) was confirmed in some of the indolylmethylene-2-indolinones.