Showing papers by "Giuseppe Paglietti published in 1998"
TL;DR: 12 quinoxalines bearing a methyleneanilino or methyleneaminobenzoylglutamate group on position 6 of the ring proved to be less potent inhibitors of tumor cells than other classical and non-classical antifolate analogues previously described by us.
Abstract: Eighteen quinoxalines bearing a methyleneanilino or methyleneaminobenzoylglutamate group on position 6 of the ring and various lipophilic substituents on positions 2 and 3 were prepared in order to discover if their structural analogy with both trimetrexate (TMQ) and 10-propargyl-5,8-dideazafolic acid (CB 3717) might display in vitro anticancer activity. Among these, 12 compounds were selected at the National Cancer Institute, Bethesda, MD, USA; they exhibited moderate (4b,d,i,l,m and 8) to strong (4f,h and 5a,e) cell-growth inhibition at a concentration of 10−4 M. Interesting selectivities were also recorded between 10−8 and 10−6 M. These analogues proved to be less potent inihibitors of tumor cells than other classical and non-classical antifolate analogues previously described by us.
24 citations
TL;DR: Inhibitory activity against dihydrofolate reductase (DHFR) (bovine and rat liver) was determined for the most active compounds and showed that this type of quinoxaline exhibited an appreciable activity in comparison with the previously described aza analogues.
Abstract: Twenty-four out of twenty-nine quinoxalines were selected at the National Cancer Institute, Bethesda, Md, USA, for in vitro anticancer screening. Among these, 10 derivatives exhibited high values of percent tumor growth inhibition at a concentration of 10−4 M in all cancer cell lines. Four of these compounds maintained these values at 10−5 M, whereas a certain number exhibited significant values of percent inhibition at the most diluted concentrations (10−8 – 10−6 M). Inhibitory activity against dihydrofolate reductase (DHFR) (bovine and rat liver) was determined for the most active compounds. This test showed that this type of quinoxaline exhibited an appreciable activity in comparison with the previously described aza analogues. In the other test (Lactobacillus casei, thymidylate synthase (TS), human HTS) no or poor activity was detected in both series of compounds.
23 citations
TL;DR: Comparison of the presently observed activity with that of the previously described aza-analogues confirms that the effected isosteric substitution is highly valuable in some cases.
Abstract: Among twenty-eight novel compounds (twenty-two 2,3-disubstituted-6-[(substituted-phenoxy)methyl-quinoxalines and six 4-[(2,3-disubstituted-quinoxalin-6-yl)methoxy]benzoylglutamates ) only thirteen were selected at NCI for evaluation of their in vitro anticancer activity. The results have shown that compounds 3l,c,b,e and 4b were endowed with significantly high values of percent tumor growth inhibition on several tumor cell lines at 10(-4) M, while compound 3t was characterized by a high selectivity, being still strongly inhibiting on three cell lines at 10(-5) M. Comparison of the presently observed activity with that of the previously described aza-analogues confirms that the effected isosteric substitution is highly valuable in some cases.
20 citations
TL;DR: Results obtained in this series seem to indicate that in general carboxy or carboethoxy groups close to O-link with phenyl or benzoyl glutamates on position 2 are detrimental for anticancer activity.
Abstract: Thirty quinoxalines bearing a substituted phenoxy or hydroxybenzoylglutamate group on position 2, a carboethoxy or carboxy group on position 3 and a trifluoromethyl group on position 6 or 7 of the heterocycle were prepared in order to evaluate the in vitro anticancer activity. Screening over 21 compounds selected at the National Cancer Institute (Bethesda, MD) showed that only few derivatives exhibited a moderate growth inhibition activity on various tumor panel cell lines at 10 −4 molar concentration. The acid derivatives showed no growth inhibition activity. The results obtained in this series seem to indicate that in general carboxy or carboethoxy groups close to O-link with phenyl or benzoyl glutamates on position 2 are detrimental for anticancer activity.
14 citations
TL;DR: A series of various bis(hydroxymethyl) carbamate derivatives of 7-mono- and 7,8-disubstituted-1-methyl-benzo[g]indoles was prepared in order to evaluate their cytostatic and cytotoxic activities in vitro.
Abstract: A series of various bis(hydroxymethyl) carbamate derivatives of 7-mono- and 7,8-disubstituted- l-methyl-benzo[g]indoles was prepared in order to evaluate their cytostatic and cytotoxic activities in vitro. Compounds 2a-h showed significant tumor growth inhibition activity and were more potent than the 4,5-dihydrobenzo[g] indole analogues previously described. Compound 2a was the most active in this series, showing high activity and selectivity for some human cancer cell lines in the National Cancer Institute screen.
9 citations
TL;DR: Preliminary screening performed at NCI showed that most derivatives exhibited a moderate to strong growth inhibition activity on various tumor panel cell lines between 10(-5) and 10(-4) molar concentrations.
Abstract: Thirty quinoxalines bearing a substituted anilino group on position 2, a carboethoxy or carboxy group on position 3 and a trifluoromethyl group on position 6 or 7 of the heterocycle were prepared in order to evaluate in vitro anticancer activity. Preliminary screening performed at NCI showed that most derivatives exhibited a moderate to strong growth inhibition activity on various tumor panel cell lines between 10(-5) and 10(-4) molar concentrations. Interesting selectivities were also recorded between 10(-8) and 10(-6) M for a few compounds. One single compound exhibited good activity against Candida albicans.
3 citations
1 citations
TL;DR: A series of bis(hydroxymethyl) carbamate derivatives of 7-mono and 7,8-disubstituted l-methyl-benzo[g]indoles was prepared in order to evaluate their cytostatic and cytotoxic activities in vitro as mentioned in this paper.
Abstract: A series of various bis(hydroxymethyl) carbamate derivatives of 7-mono- and 7,8-disubstituted- l-methyl-benzo[g]indoles was prepared in order to evaluate their cytostatic and cytotoxic activities in vitro. Compounds 2a-h showed significant tumor growth inhibition activity and were more potent than the 4,5-dihydrobenzo[g] indole analogues previously described. Compound 2a was the most active in this series, showing high activity and selectivity for some human cancer cell lines in the National Cancer Institute screen.
TL;DR: Among twenty-eight novel compounds (twenty-two 2,3-disubstituted-6-[(substitized-phenoxy)methyl-quinoxalines and six 4]-(2,3 disubstitized -quinoxalin-6-yl)methoxy]benzoylglutamates ) only thirteen were selected at NCI for evaluation of their in vitro anticancer activity as discussed by the authors.
Abstract: Among twenty-eight novel compounds (twenty-two 2,3-disubstituted-6-[(substituted-phenoxy)methyl-quinoxalines and six 4-[(2,3-disubstituted-quinoxalin-6-yl)methoxy]benzoylglutamates ) only thirteen were selected at NCI for evaluation of their in vitro anticancer activity. The results have shown that compounds 3l,c,b,e and 4b were endowed with significantly high values of percent tumor growth inhibition on several tumor cell lines at 10(-4) M, while compound 3t was characterized by a high selectivity, being still strongly inhibiting on three cell lines at 10(-5) M. Comparison of the presently observed activity with that of the previously described aza-analogues confirms that the effected isosteric substitution is highly valuable in some cases.