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Investigation of the molecular reactivity of bioactive oxiranylmethyloxy anthraquinones
Author(s) -
Ribaudo Giovanni,
Ongaro Alberto,
Zorzan Maira,
Pezzani Raffaele,
Redaelli Marco,
Zagotto Giuseppe,
Memo Maurizio,
Giacelli Alessandra
Publication year - 2019
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201900030
Subject(s) - anthraquinones , chemistry , bifunctional , reactivity (psychology) , covalent bond , combinatorial chemistry , adduct , anthraquinone , nucleic acid , hsab theory , nucleobase , dna , molecule , stereochemistry , organic chemistry , biochemistry , medicine , botany , alternative medicine , pathology , biology , catalysis
The design of a multitarget and multifunctional small molecule containing two functional groups reacting through different mechanisms represents an attractive goal for the medicinal chemist. The preparation of two bifunctional oxiranylmethyloxy anthraquinones, previously investigated as anticancer agents, is described here. These compounds combine a planar, DNA‐intercalating and pro‐oxidant anthraquinone scaffold and the alkylating epoxide functions which can covalently react with the nucleic acid. Their multilevel molecular reactivity was studied through a combination of analytical techniques: The DNA‐binding properties were investigated using a mass spectrometry‐based binding assay and by nuclear magnetic resonance, highlighting the formation of a covalent adduct with a nucleobase. Moreover, the contribution of the pro‐oxidant redox cycling was evaluated.