Protoflavones represent a rare, unique class of naturally occurring bioactive flavonoid derivatives. Recent publications revealed their antiviral, anti-angiogenic and cytotoxic activity, moreover they have also been found to interfere with crucial DNA damage response mechanisms[1-3]. The pharmacophore of these compounds is the non-aromatic B-ring – the unusual p-quinol moiety. The formation of this moiety can be synthetically achieved from 4 ʹ -hydroxyflavones applying hypervalent iodine reagents.
Chalcones – also abundant in nature – exert anti-inflammatory, antioxidant, antibacterial and anticancer activity; anti-angiogenic effect of 4-hydroxychalcone 3 was reported lately.
During the current project our aim is - in order to broaden our knowledge on structure-activity relationships concerning protoflavones - to build a compound library by synthesizing and characterizing variously substituted chalcone analogues bearing the p-quinol moiety.
The key intermedier 4-hydroxychalcone 3 was synthesysed via Claisen-Schmidt condensation. Seven new compounds (4-10) were subsequently obtained by oxidative dearomatization performed with PIFA in various solvent mixtures. These compounds are expected to exert potent antitumor activity; their bioactivity testing is currently in progress.
This work was supported by the NKFIH, Hungary (K119770), the EU-funded Hungarian grant EFOP-3.6.1- 16-2016-00008, and GINOP-2.3.2-15-2016-00012. A.H. acknowledges the János Bolyai fellowship of the Hungarian Academy of Sciences and the Kálmán Szász Prize.
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