Synthesis, Conformational Analysis and ctDNA Binding Studies of Flavonoid Analogues Possessing the 3,5-di-<i>tert</i>-butyl-4-hydroxyphenyl Moiety
Andromachi Tzani,
Eftichia Kritsi,
Lamprini Tsamantioti,
Ioanna Kostopoulou,
Maria-Anna Karadendrou,
Panagiotis Zoumpoulakis,
Anastasia Detsi
Affiliations
Andromachi Tzani
Laboratory of Organic Chemistry, Department of Chemical Sciences, School of Chemical Engineering, National Technical University of Athens, Heroon Polytechniou 9, Zografou Campus, 15780 Athens, Greece
Eftichia Kritsi
Institute of Chemical Biology, National Hellenic Research Foundation, 48, Vas. Constantinou Avenue, 11635 Athens, Greece
Lamprini Tsamantioti
Laboratory of Organic Chemistry, Department of Chemical Sciences, School of Chemical Engineering, National Technical University of Athens, Heroon Polytechniou 9, Zografou Campus, 15780 Athens, Greece
Ioanna Kostopoulou
Laboratory of Organic Chemistry, Department of Chemical Sciences, School of Chemical Engineering, National Technical University of Athens, Heroon Polytechniou 9, Zografou Campus, 15780 Athens, Greece
Maria-Anna Karadendrou
Laboratory of Organic Chemistry, Department of Chemical Sciences, School of Chemical Engineering, National Technical University of Athens, Heroon Polytechniou 9, Zografou Campus, 15780 Athens, Greece
Panagiotis Zoumpoulakis
Institute of Chemical Biology, National Hellenic Research Foundation, 48, Vas. Constantinou Avenue, 11635 Athens, Greece
Anastasia Detsi
Laboratory of Organic Chemistry, Department of Chemical Sciences, School of Chemical Engineering, National Technical University of Athens, Heroon Polytechniou 9, Zografou Campus, 15780 Athens, Greece
Flavanones and their biochemical precursors, chalcones, are naturally occurring compounds and consist of privileged scaffolds used in drug discovery due to their wide range of biological activities. In this work, two novel flavanones (3 and 4), the arylidene flavanone 5, and the chalcone 6, displaying structural analogies with butylated hydroxytoluene (BHT), were synthesized via an aldol reaction. According to the antioxidant activity studies of the synthesized flavanones, the arylidene flavanone 5 was the most potent antioxidant (70.8% interaction with DPPH radical and 77.4% inhibition of lipid peroxidation). In addition, the ability of the synthesized compounds to bind with ctDNA was measured via UV-spectroscopy, revealing that chalcone 6 has the strongest interaction with DNA (Kb = 5.0 × 10−3 M−1), while molecular docking was exploited to simulate the compound-DNA complexes. In an effort to explore the conformational features of the novel synthetic flavanones (3 and 4), arylidene flavanone 5, and chalcone 6, theoretical calculations were applied and the calculation of their physicochemical properties was also performed.
