In 2021, our research group published the prominent anticancer activity achieved through
the successful combination of two redox centres (ortho-quinone/para-quinone or quinone/seleniumcontaining triazole) through a copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The
combination of two naphthoquinoidal substrates towards a synergetic product was indicated, but
not fully explored. Herein, we report the synthesis of 15 new quinone-based derivatives prepared
from click chemistry reactions and their subsequent evaluation against nine cancer cell lines and
the murine fibroblast line L929. Our strategy was based on the modification of the A-ring of paranaphthoquinones and subsequent conjugation with different ortho-quinoidal moieties. As anticipated,
our study identified several compounds with IC50 values below 0.5 µM in tumour cell lines. Some
of the compounds described here also exhibited an excellent selectivity index and low cytotoxicity
on L929, the control cell line. The antitumour evaluation of the compounds separately and in their
conjugated form proved that the activity is strongly enhanced in the derivatives containing two
redox centres. Thus, our study confirms the efficiency of using A-ring functionalized para-quinones
coupled with ortho-quinones to obtain a diverse range of two redox centre compounds with potential
applications against cancer cell lines. Here as well, it literally takes two for an efficient tango