The Correlation between Chemical Structures and Antioxidant, Prooxidant, and Antitrypanosomatid Properties of Flavonoids

Abstract

Flavonoids have demonstrated in vivo and in vitro leishmanicidal, trypanocidal, antioxidant, and prooxidant properties. The chemotherapy of trypanosomiasis and leishmaniasis lacks efficacy, presents high toxicity, and is related to the development of drug resistance. Thus, a series of 40 flavonoids were investigated with the purpose of correlating these properties via structure and activity analyses based on integrated networks and QSAR models. The classical groups for the antioxidant activity of flavonoids were combined in order to explain the influence of antioxidant and prooxidant activities on the antiparasitic properties. These analyses become useful for the development of efficient treatments for leishmaniasis and trypanosomiasis. Finally, the dual activity of flavonoids presenting both anti- and prooxidant activities revealed that the existence of a balance between these two features could be important to the development of adequate therapeutic strategies.

Host-Directed Drug Therapies for Neglected Tropical Diseases Caused by Protozoan Parasites

“…Curcumin in particular has been shown to have immunomodulatory effects on the host, preventing damage caused by the generation of ROS ( Wolkmer et al, 2013 ). Gallic acid and quercetin both have also been shown to have prooxidant effects, leading to a direct trypanocidal effects by generation of excess ROS while also maintaining the host protective antioxidant effects ( Baldim et al, 2017 ). Several of these compounds have also been identified as having inhibitory effects against T. brucei RNA triphosphatase ( Smith et al, 2016 ).…”

Antimicrobial O-Alkyl Derivatives of Naringenin and Their Oximes Against Multidrug-Resistant Bacteria

“…Alternatively, there are some data showing that naringenin is implicated in the inhibition of efflux pumps, which are proteins involved in the outflow of antibiotics from microbial cells [ 44 , 51 ]. It is also important to indicate that due to its strong antioxidant properties, naringenin has a high capacity to neutralise reactive oxygen species (ROS) [ 52 ], which are generated by some antibiotics, e.g., aminoglycosides, glycopeptides, or fluoroquinolones [ 53 , 54 ]. For example, it has been demonstrated with the use of gentamicin that various flavonoid compounds have the ability to reduce the oxidative stress-related toxicity of antibiotics against eukaryotic cells, without affecting their bactericidal activity [ 55 ].…”

HPLC-Based Activity Profiling for Antiprotozoal Compounds in Croton gratissimus and Cuscuta hyalina

“…The influence of a balance between antioxidant and prooxidant properties of flavonoids on antiparasitic activity, and a correlation with their chemical structure has been investigated with the aid of QSAR models ( Baldim et al., 2017 ). Compounds that displayed moderate to higher antitrypanosomal activity shared structural features, such as Δ 2,3 unsaturation, presence of a hydroxyl group at C-3, a carbonyl group at C-4, and a catechol moiety in ring B.…”