Maria Teresa Cocco

Design, synthesis, and in vitro antitumor activity of new 1,4-diarylimidazole-2-ones and their 2-thione analogues

A series of new 1,4-diarylimidazol-2(3H)-one derivatives and their 2-thione analogues has been prepared and evaluated in vitro for antitumor activity against the NCI human cancer cell panel. Compounds bearing a 3,4,5-trimethoxyphenyl ring linked to either N-1 or C-4 position of the imidazole core demonstrated an interesting profile of cytotoxicity with preferential activity against leukemic cell lines. Compound 13 exhibited a potent antitumor activity against MOLT-4 (GI(50)=20 nM) and SR (GI(50)=32 nM) cell lines.

Thyroid hormone (T3) and TRβ agonist GC-1 inhibit/reverse nonalcoholic fatty liver in rats

Nonalcoholic fatty liver disease is the most common noninfectious liver disease in clinical practice, and there is an increasing need for new therapeutic approaches for the treatment of this liver disease. Here, we examined the effect of the thyroid hormone triiodothyronine (T3) and the agonist of the thyroid hormone receptor β isoform (TRβ), GC‐1, on fatty liver and steatohepatitis induced in rodents by a choline‐methionine deficient (CMD) diet. Male Fischer 344 rats fed a CMD diet for 1 wk developed a marked fatty liver and mild hepatitis. Concurrent administration of T3 resulted in a complete prevention of the fatty change associated with increased fatty acid mitochondrial and peroxisomal β‐oxidation. To investigate whether T3 could also reverse fully established fatty liver, rats were fed a CMD diet for 10 wk and then cofed T3 for 1 wk. Coadministration of T3 resulted in a complete regression of liver steatosis associated with a decrease of lipid peroxidation, cyclooxygenase‐2 expression, and activation of phospho‐STAT3 and phospho‐SAPK/JNK. Finally, additional experiments showed that GC‐1, which has no significant side effects on heart rate, prevented and reverted CMD‐induced fat accumulation, and ameliorated steatohepatitis. These results indicate that TR agonists have the potential to inhibit or reverse hepatic steatosis induced by a nutritional model.—Perra, A., Simbula, G., Simbula, M., Pibiri, M., Kowalik, M. A., Sulas, P., Cocco, M. T., Ledda‐Columbano, G. M., Columbano, A. Thyroid hormone (T3) and TRβ agonist GC‐1 inhibit/reverse nonalcoholic fatty liver in rats. FASEB J. 22, 2981–2989 (2008)

Synthesis and evaluation of anticancer activity of 2-arylamino-6-trifluoromethyl-3-(hydrazonocarbonyl)pyridines.

The synthesis and anticancer activity of 2-arylamino-6-trifluoromethyl-3-(hydrazonocarbonyl)pyridines is described. The new trifluoromethylpyridine derivatives were evaluated for their anticancer activity toward human cancer cell lines by the National Cancer Institute (NCI). Most of them had excellent growth inhibition activity, having GI(50) values in the low micromolar to nanomolar concentration range. The most potent 2,6-dichlorobenzaldehydehydrazone 29 inhibited the growth of all tested cancer cell lines with nanomolar potency, and did not show animal toxicity. Hydrazone 29 has been selected by the Biological Evaluation Committee of NCI for testing in vivo Hollow Fiber Assay.

Synthesis of ibuprofen heterocyclic amides and investigation of their analgesic and toxicological properties

A series of amides of ibuprofen with heteroaromatic amines was synthesized and assayed in vivo for their analgesic properties by means of writhing test in rats. When compared to parent ibuprofen some of the new amides exhibited a comparable or improved analgesic activity and a lower ulcerogenic effect.

Synthesis and antimycobacterial activity of some isonicotinoylhydrazones

Abstract Aseries of isonicotinoylhydrazones 2 were prepared by addition of some aryloxyacetonitriles with isonicotinoylhydrazine in basic medium. These compounds have been further reacted with pyridinecarboxaldehydes to give the corresponding pyridylmethyleneamino derivatives 3 – 5 . The new synthesized hydrazones and their pyridylmethyleneamino derivatives were tested for their activity against mycobacteria, Gram-positive and Gram-negative bacteria. The cytotoxicity was also tested. Several compounds showed a good activity against Mycobacterium tuberculosis H37Rv and some isonycotinoylhydrazones 2 showed a moderate activity against a clinically isolated M. tuberculosis which was isoniazid resistant.

Synthesis and antitumour activity of 4-hydroxy-2-pyridone derivatives.

4-hydroxy-2-pyridone derivatives 2 were prepared by reaction of 3-amino-3-dialkylaminopropenoates with bis(2,4, 6-trichlorophenyl)malonate. These compounds were further reacted with a set of aldehydes to give bis(pyridyl)methanes 3 and 4. The newly synthesized compounds 2, 3 and 4 were evaluated in vitro as antitumour agents against 60 human tumour cell lines. Some derivatives exhibit tumour growth inhibition activity. In particular, derivative 4g, the most active of the series, possesses significant activity on all cell lines at concentrations ranging from 1 x 10(-6) to 1 x 10(-5) M.

Synthesis and antimycobacterial activity of new S-alkylisothiosemicarbazone derivatives

A new series of S-alkylisothiosemicarbazones of 3- and 4-pyridincarboxaldehyde and 4-fluoro- and 4-trifluoromethylbenzaldehyde was synthesized and evaluated for biological activity against various Mycobacterium strains. Inhibitory activity against Mycobacterium tuberculosis H37Rv ATCC 27294 and INH-R ATCC 35822 was compared with activity against clinical isolated Mycobacteria as well as against MOTT. Some of newly prepared compounds showed best inhibitory values against clinical isolated Mycobacteria, besides to low citotoxicity values.

Synthesis and in vitro antitumoral activity of new N-phenyl-3-pyrrolecarbothioamides.

A new series of N-phenylpyrrolecarbothioamides were obtained from base catalyzed intramolecular cyclization of 3-amino-3-(alkyl or arylamino)propenethioamides. Pyrrole derivatives were evaluated for their in vitro anticancer activity toward cell lines of nine different types of human cancer. Some of newly prepared compounds demonstrated inhibitory effects on the growth of a wide range of cancer cell lines generally at 10(-6) M level and in some case at 10(-8) M concentrations.

New bis(pyridyl)methane derivatives from 4-hydroxy-2-pyridones: synthesis and antitumoral activity

Bis(pyridyl)methane derivatives 5-40 were obtained from the reaction of 4-hydroxy-2-pyridones 3 and 4 with aldehydes. Compounds 5-40 were evaluated for cytotoxic activity against a panel of 60 human cancer cell lines by the National Cancer Institute and some of them demonstrated inhibitory effects on the growth of a wide range of cancer cell lines generally at 10(-5) M level and in some case at 10(-7) M concentrations.

2-Acylhydrazino-5-arylpyrrole derivatives: synthesis and antifungal activity evaluation.

The synthesis and antifungal activity of 2-acylhydrazino-5-arylpyrroles 21-62 are described. Pyrrole derivatives 21-62 were evaluated for their antifungal activity towards Candida albicans ATCC 10231 and three Candida non-albicans isolated from clinical specimens. Most of them showed very good antifungal activities against Candidae, having MIC values in the 0.39-3.12 microg/mL range and enhanced inhibition potency as compared to that of fluconazole. In addition, some of the most active compounds were tested for cytotoxic activities against breast (MCF-7), lung (H-460), and central nervous system (SF-268) human cancer cell lines with the NCI anticancer drug screen. The activity of pyrroles described in this paper, along with the low toxicity, shows promise for the future development of non-toxic new antimycotic agents. The relationship between functional group variation and biological activity of the evaluated compounds is also discussed.