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Development of Naphthalimide DNA Intercalators as Anticancer Therapeutics
Author(s) -
Skubic Kristin,
Adams Miranda,
Horn Jill,
Priddy Anna,
Oelrich Renae,
Lewis Michael,
Znosko Brent,
Arnatt Christopher
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb535
Subject(s) - intercalation (chemistry) , skbr3 , topoisomerase , chemistry , dna , stereochemistry , small molecule , molecule , biochemistry , combinatorial chemistry , cancer cell , cancer , biology , genetics , human breast , organic chemistry
In the past decade, there has been substantial progress in research of small molecule DNA intercalators as antineoplastic agents. Due to specificity of the DNA‐intercalator interaction, compounds may be tailored to target specific genes to avoid potential side effects. For this research, derivatives of 3‐amino‐1, 8‐naphthalic anhydride were synthesized (initial research by Braña et al ) with combination of different amino arms and substituents along the 3‐ or 4‐ position generating a series of naphthalimide derivatives to determine if compound structure influenced DNA intercalation (via DNA melt studies), antiproliferative activities (standard breast cancer cell lines SKBR3, MDAMB231, and MCF‐7), and topoisomerase II inhibition activity. Calculated lethal dose (LD 50 ) values for the antiproliferation assays (ranging from low nM to low μM), DNA melt studies, and topoisomerase II inhibition activities illustrate a clear structure‐activity relationship for this series of naphthalimides.