Rhodium-catalyzed C-H bond activation for the synthesis of quinonoid compounds: Significant Anti-Trypanosoma cruzi activities and electrochemical studies of functionalized quinones

Abstract

Thirty four halogen and selenium-containing quinones, synthesized by rhodium-catalyzed C-H bond activation and palladium-catalyzed cross-coupling reactions, were evaluated against bloodstream trypomastigotes of T. cruzi. We have identified fifteen compounds with IC/24 h values of less than 2 μM. Electrochemical studies on A-ring functionalized naphthoquinones were also performed aiming to correlate redox properties with trypanocidal activity. For instance, (E)-5-styryl-1,4-naphthoquinone 59 and 5,8-diiodo-1,4-naphthoquinone 3, which are around fifty fold more active than the standard drug benznidazole, are potential derivatives for further investigation. These compounds represent powerful new agents useful in Chagas disease therapy.

Synthesis of Selenium-Quinone Hybrid Compounds with Potential Antitumor Activity via Rh-Catalyzed C-H Bond Activation and Click Reactions

“…Recently, our research group developed methodologies which enable the functionalization of quinones via rhodium catalyzed C-H activation [ 46 , 47 ], paving the way to new molecules containing iodine, bromine and selenium atoms with remarkable biological activity [ 48 ]. Encouraged by that fact, the same catalyst system was explored with other electrophilic selenium sources, focusing on obtaining new molecules with a substituent in the phenyl selenium moiety.…”

Anti-tubercular profile of new selenium-menadione conjugates against Mycobacterium tuberculosis H37Rv (ATCC 27294) strain and multidrug-resistant clinical isolates

“…For example, using N -(phenylseleno)-phthalimide or phenyl hypochloroselenoites as an electrophile, the C-2 selenation of naphthoquinone can be performed, as well as the Rh-catalyzed selenation of benzoquinone ( Fig. 2 A) [ [37] , [38] , [39] ].

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Characterization and trypanocidal activity of a β-lapachone-containing drug carrier

“…The results are expressed as the difference in the percent reduction between treated and untreated cells, with the LC 50 being the concentration that leads to damage of 50% of the mammalian cells. The selectivity index (SI) was calculated by the ratio between the LC 50 and IC 50 , the latter of which was the concentration that led to 50% lysis/proliferation inhibition of the parasites [45].…”