Furanaphthoquinones are well known in medicinal chemistry for exhibiting relevant structural heterogeneity and bioactivities. In this work, it was synthesized a series of furanaphthoquinones through a tandem reaction between lawsone (8) and cyclic ketones in the presence of morpholine. This strategy provides an efficient and general method for synthesizing furanaphthoquinones with activity against the epimastigote form of Trypanosoma cruzi (T. cruzi), the parasite that causes Chagas disease. Compound 9b was the better prototype, and it exhibited high potency for causing parasite death, showed reduced acute toxicity towards mammalian cells, and was capable of rupturing the epimastigote plasma membrane and acting on sterol 14α-demethylase (CYP51). Additionally, 9b reduced trypomastigote viability by 99% after 24 h. Candidate 9b demonstrated the best and most promising profile when bound to CYP51.

Electrochemical methods are powerful in the characterization and design of redox-modulating agents. We, herein, report the electrochemical investigation, in aprotic medium, of eleven synthetic 3-thio-substituted-nor-beta-lapachones, along with the determination of cytotoxic activity and correspondent selectivity index, against several cancer cell lines and one normal cell. Four of the quinones are novel compounds. The redox behavior is representative of two independent systems: the easy reduction of the quinone moiety and, at far more negative potential, the reductive cleavage of the C-S-C bonding; and the anodic part controlled by the oxidation of the sulfur moiety. The compounds have shown relevant cytotoxic activity, with emphasis on 3-phenyl-thio-2,2-dimethyl-2,3-dihydronaphtho[1,2-b]furan-4,5-dione (compound 2), which mechanism of molecular action was shown to be related to reactive oxygen species (ROS) release. Despite the absence of a linear correlation, there is a trend: the majority of the thionaphthoquinones, with values of first wave reduction potential, less negative than -0.65 V, were active. The less electrophilic compound (3-(cyclohexylthio)-2,2-dimethyl-2,3-dihydronaphtho[1,2-b]furan-4,5-dione, cyclohexyl derivative) is also the less cytotoxic toward cancer cells. Agents containing chalcogens and quinones can be used to attack entities with a disturbed redox balance.

The synthesis of several new xanthenes based on the 1,3-dicarbonyl scaffolds lawsone and coumarin was developed using tandem three-component reactions involving the reagents ortho-hydroxybenzaldehyde, as bifunctional reagent, and an appropriate thiol. These reactions generated two series of para- and ortho-naphthoxanthenes that are structurally related to α- and β-pyranaphthoquinones and one series of coumarin-xanthene derivatives.

Vários estudos têm mostrado o potencial citotóxico de derivados da nor-β-lapachona contra células tumorais. Considerando a nor-β-lapachona um importante protótipo, uma série inédita de nor-β-lapachonas substituídas em C-3 foi sintetizada através de uma nova metodologia sintética envolvendo intermediário sintético 3-hidróxi-nor-β-lapachona para o acoplamento de alguns nucleófilos contendo núcleos derivados de carboidratos ou 2H-pirazóis. Todos os derivados foram avaliados frente a quatro linhagens de células tumorais. Duas das substâncias apresentaram moderada citotoxicidade, enquanto as demais inibiram fortemente todas as linhagens tumorais testadas.

Several studies have demonstrated the cytotoxic potential of nor-β-lapachone derivative against cancer cells. Considering nor-β-lapachone as an important prototype, a set of new 3-substituted nor-β-lapachones was synthesized by a new synthetic route that involves the use of synthetic intermediate generated for coupling with several nucleophiles containing the carbohydrate and 2H-pyrazole substituent moieties. All the compounds were screened against four tumor cell lines. Two of the compounds showed moderate cytotoxicity, while the other compounds strongly inhibit all tested cancer cell lines.