Quinoxaline chemistry. Part 10. Quinoxaline 10-oxa-analogues of trimetrexate (TMQ) and of 5,8-dideazafolic acid. Synthesis and evaluation of in vitro anticancer activity.
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.
Vitale
G
G
Istituto di Chimica Farmaceutica e Tossicologica, Università di Sassari, Italy.
Corona
P
P
Loriga
M
M
Paglietti
G
G
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D016597:Trimetrexate / Q000138:chemical synthesis* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011799:Quinazolines; D011810:Quinoxalines; C025928:CB 3705; D016597:Trimetrexate