DHFR and neoplasm: 6 Particularly, pyrido[2,3-d]pyrimidines have been shown to be effective against Toxoplasma gondii and Pneumocystis carinii (tg) culture of tumor cell lines, and the activity is attributed to dihydrofolate reductase inhibition.7–9 Due their diverse anticancer or antiproliferative properties, pyrido[2,3-d]pyrimidine derivatives were great interest of reseachers working in this field.10,11 Fusing a pyridine and a pyrimidine ring results in pyridopyrimidines, ortho-fused bicyclic heterocyclic structures.