Synthesis, Antifolate and Anticancer Activities of N(5) -Substituted 8,10-Dideazatetrahydrofolate Analogues
Chao Tian1, Zhili Zhang1, Shouxin Zhou1
1Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
Abstract:
Based on our previous work, seven N(5) -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 N(10) with carbon would significantly increase inhibitory activities against DHFR and cytotoxicities against cancer cell lines. Compound 19a with 4-amino and N(5) -formyl showed great antitumour activities against HL-60, Bel-7402 and BGC823 which were much better than MTX.
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