Metabolic and electrochemical mechanisms of dimeric naphthoquinones cytotoxicity in breast cancer cells.

Cancer cells reprogram their metabolism due to genetic alteration to compensate for increased energy demand and enhanced anabolism, cell proliferation, and protection from oxidative damage. Here, we assessed the cytotoxicity of three dimeric naphthoquinones against the glycolytic MCF-7 versus the oxidative MDA-453 breast carcinoma cell lines. Dimeric naphthoquinones 1 and 2 impaired MDA-453, but not MCF-7, cell growth at IC(50)=15 μM.

A new method for the synthesis of 2-hydroxy-3-nitro-1,4-naphthoquinones: application to regiospecific preparation of unsymmetrical nitrobiquinones.

Novel 2-hydroxy-3-nitro-1,4-naphthoquinones were synthesized by an improved method utilizing nitronium tetrafluoroborate in high yields. A subsequent conversion to 2-chloro-3-nitro-1,4-naphthoquinones and a substitution of the chlorine by hydroxyquinone anions yielded 3-nitro-2,2'-binaphthoquinones with a complete regiocontrol.

Regiocontrolled synthesis and HIV inhibitory activity of unsymmetrical binaphthoquinone and trimeric naphthoquinone derivatives of conocurvone.

Unsymmetrical biquinone and trimeric quinone derivatives were synthesized using halotriflate-biselectrophilic naphthoquinones through stepwise regioselective quinone substitution chemistry and evaluated for their ability to inhibit the cytopathogenic effects of HIV-1 using an MTT colorimetric assay. Compounds were also screened for their ability to inhibit the activity of HIV-1 integrase in vitro. Pyranylated trimeric quinones and biquinones exhibited both antiviral activity and integrase inhibitory activity.

Effect of methoxyl group position on the regioselectivity of ammonia substitution reactions involving 3,3'-dichloro-2,2'-binaphthoquinones.

A series of methoxyl-substituted 3,3'-dichloro-2,2'-binaphthoquinones 2 were prepared and evaluated for regioselectivity in ammonia substitution reactions. Biquinone 2b underwent regiospecific amination at the unsubstituted chloronaphthoquinone unit whereas the isomeric biquinone, 2c, produced moderate regioselectivity (85:15). Biquinone 2d, however, showed no level of regioselectivity demonstrating that the position of the methoxyl group influences the regiochemistry.

Regiocontrolled synthesis of the trimeric quinone framework of conocurvone.

[reaction: see text] The trimeric quinone framework of conocurvone is crucial for its potent anti-HIV activity. A new synthesis of trimeric quinones based on stepwise substitution of the halogens in 2,3-dihaloquinones by hydroxyquinone anions is described. Chlorinated biquinones are key intermediates that undergo regiospecific substitution reactions to yield trimeric quinone monomethyl ethers.