Synthesis, Antifolate and Anticancer Activities of N5-Substituted 8,10-Dideazatetrahydrofolate Analogues

Abstract

Based on our previous work, seven N5-substituted 8,10-dideazatetrahydrofolate analogues and one 8-deazatetrahydrofolate analogue were designed and synthesized as human dihydrofolate reductase (hDHFR) inhibitors. All compounds were assayed versus DHFR and five different cancer cell lines. The biological assay indicated that replacing N10 with carbon would significantly increase inhibitory activities against DHFR and cytotoxicities against cancer cell lines. Compound 19a with 4-amino and N5-formyl showed great antitumour activities against HL-60, Bel-7402 and BGC823 which were much better than MTX.