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Synthesis, Antifolate and Anticancer Activities of N 5 ‐Substituted 8,10‐Dideazatetrahydrofolate Analogues
Author(s) -
Tian Chao,
Zhang Zhili,
Zhou Shouxin,
Yuan Mengmeng,
Wang Xiaowei,
Liu Junyi
Publication year - 2016
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12681
Subject(s) - antifolate , stereochemistry , chemistry , combinatorial chemistry , antimetabolite , organic chemistry , toxicity
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 BGC 823 which were much better than MTX .