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Discovery of a more potent anticancer agent than C4 ‐benzazole 1,8‐naphthalimide derivatives against murine melanoma
Author(s) -
Tung ChiHua,
Lu YenTa,
Kao WeiTing,
Liu JenWei,
Lai YiHsuan,
Jiang ShinnJong,
Chen HaoPing,
Shih TzengeLien
Publication year - 2020
Publication title -
journal of the chinese chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.329
H-Index - 45
eISSN - 2192-6549
pISSN - 0009-4536
DOI - 10.1002/jccs.202000019
Subject(s) - chemistry , moiety , stereochemistry , topoisomerase , potency , in vitro , lead compound , docking (animal) , melanoma , ethylenediamine , combinatorial chemistry , biochemistry , cancer research , organic chemistry , medicine , nursing , biology
Three novel naphthalimide‐based derivatives were synthesized and tested in vitro as anticancer agents. Our previous report of the C4‐benzazole 1,8‐naphthalimide derivatives showed good inhibition against murine melanoma. We aimed to synthesize more potent agents and found that compound 5 reported in this article behaved 5‐ to 10‐fold potency than our previous best results. The unique structure of compound 5 consisted of a naphthalimide framework in which C4 position was linked with an ethylenediamine group where the amino group was coupled with a 2‐piconic acid moiety. Compound 5 exhibited the most potent inhibitory activity toward human DNA topoisomerase II proteins with IC 50 value (2.6 ± 0.1 μM) against murine B16F10 melanoma cells among the three target compounds synthesized in this study. In accordance with this finding, the results of molecular docking also revealed that compound 5 has the highest affinity with human DNA topoisomerase II among the selected compounds. Compound 5 , therefore, has high potential for becoming a lead compound.