title: Synthesis, Antifolate and Anticancer Activities of N(5) -Substituted 8,10-Dideazatetrahydrofolate Analogues.
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.
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Tian
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
authors.forename: Zhili
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
authors.forename: Shouxin
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Yuan
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.|State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China.
authors.forename: Junyi
authors.initials: J
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D005493:Folic Acid Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000970:Antineoplastic Agents; D005493:Folic Acid Antagonists
keywords: 8,10-Dideazatetrahydrofolate; anticancer agents