The Antifungal Activity of Naphthoquinones: An Integrative Review.

Naphthoquinones are the most commonly occurring type of quinones in nature. They are a diverse family of secondary metabolites that occur naturally in plants, lichens and various microorganisms. This subgroup is constantly being expanded through the discovery of new natural products and by the synthesis of new compounds via innovative techniques. Interest in quinones and the search for new biological activities within the members of this class have intensified in recent years, as evidenced by the evaluation of the potential antimicrobial activities of quinones. Among fungi of medical interest, yeasts of the genus Candida are of extreme importance due to their high frequency of colonization and infection in humans. The objective of this review is to describe the development of naphthoquinones as antifungals for the treatment of Candida species and to note the most promising compounds. By using certain criteria for selection of publications, 68 reports involving both synthetic and natural naphthoquinones are discussed. The activities of a large number of substances were evaluated against Candida albicans as well as against 7 other species of the genus Candida. The results discussed in this review allowed the identification of 30 naphthoquinones with higher antifungal activities than those of the currently used drugs.

Characterization and trypanocidal activity of a ß-lapachone-containing drug carrier.

The treatment of Chagas disease (CD), a neglected parasitic condition caused by Trypanosoma cruzi, is still based on only two drugs, nifurtimox (Nif) and benznidazole (Bz), both of which have limited efficacy in the late chronic phase and induce severe side effects. This scenario justifies the continuous search for alternative drugs, and in this context, the natural naphthoquinone ß-lapachone (ß-Lap) and its derivatives have demonstrated important trypanocidal activities. Unfortunately, the decrease in trypanocidal activity in the blood, high toxicity to mammalian cells and low water solubility of ß-Lap limit its systemic administration and, consequently, clinical applications. For this reason, carriers as drug delivery systems can strategically maximize the therapeutic effects of this drug, overcoming the above mentioned restrictions. Accordingly, the aim of this study is to investigate the in vitro anti-T. cruzi effects of ß-Lap encapsulated in2-hydroxypropyl-ß-cyclodextrin (2HP-ß-CD) and its potential toxicity to mammalian cells.

α- and ß-Lapachone Isomerization in Acidic Media: Insights from Experimental and Implicit/Explicit Solvation Approaches.

Combined experimental and mixed implicit/explicit solvation approaches were employed to gain insights into the origin of switchable regioselectivity of acid-catalyzed lapachol cyclization and α-/ß-lapachone isomerization. It was found that solvating species under distinct experimental conditions stabilized α- and ß-lapachone differently, thus altering the identity of the thermodynamic product. The energy profile for lapachol cyclization revealed that this process can occur with low free-energy barriers (lower than 8.0 kcal mol-1 ). For α/ß isomerization in a dilute medium, the computed enthalpic barriers are 15.1 kcal mol-1 (α→ß) and 14.2 kcal mol-1 (ß→α). These barriers are lowered in concentrated medium to 11.5 and 12.6 kcal mol-1 , respectively. Experimental determination of isomers ratio was quantified by HPLC and NMR measurements. These findings provide insights into the chemical behavior of lapachol and lapachone derivatives in more complex environments.