title: Quinoxaline chemistry. Part 9. Quinoxaline analogues of trimetrexate (TMQ) and 10-propargyl-5,8-dideazafolic acid (CB 3717) and its precursors. Synthesis and evaluation of in vitro anticancer activity.
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 inhibitors of tumor cells than other classical and non-classical antifolate analogues previously described by us.
authors.affiliation: Istituto di Chimica Farmaceutica e Tossicologica, Università di Sassari, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Loriga
authors.forename: G
authors.initials: G
authors.lastname: Vitale
authors.forename: G
authors.initials: G
authors.lastname: Paglietti
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D005492:Folic Acid / Q000031:analogs & derivatives* / 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
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D011810:Quinoxalines; C031662:CB 3717; D005492:Folic Acid; D016597:Trimetrexate