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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/selenium-containing 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 para-naphthoquinones 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! [ABSTRACT FROM AUTHOR]

Although the clinical use of targeted gene sequencing-based diagnostics is valuable, whole-exome sequencing has also emerged as a successful diagnostic tool in molecular genetics laboratories worldwide. Molecular genetic tests for episodic ataxia type 2 (EA2) usually target only the specific calcium channel gene (CACNA1A) that is known to cause EA2. In cases where no mutations are identified in the CACNA1A gene, it is important to identify the causal gene so that more effective treatment can be prioritized for patients. Here we present a case of a proband with a complex episodic ataxias (EA)/seizure phenotype with an EA-affected father; and an unaffected mother, all negative for CACNA1A gene mutations. The trio was studied by whole-exome sequencing to identify candidate genes responsible for causing the complex EA/seizure phenotype. Three rare or novel variants in Sodium channel α2-subunit; SCN2A (c.3973G>T: p.Val1325Phe), Potassium channel, Kv3.2; KCNC2 (c.1006T>C: p.Ser336Pro) and Sodium channel Nav1.6; SCN8A (c.3421C>A: p.Pro1141Thr) genes were found in the proband. While the SCN2A variant is likely to be causal for episodic ataxia, each variant may potentially contribute to the phenotypes observed in this family. This study highlights that a major challenge of using whole-exome/genome sequencing is the identification of the unique causative mutation that is associated with complex disease. [ABSTRACT FROM AUTHOR]