X-ray Structure Determination, Antioxidant Voltammetry Studies of Butein and 2′,4′-Dihydroxy-3,4-dimethoxychalcone. Computational Studies of 4 Structurally Related 2′,4′-diOH Chalcones to Examine Their Antimalarial Activity by Binding to Falcipain-2

Abstract

Malaria is a huge global health burden with resistance to currently available medicines resulting in the search for newer antimalarial compounds from traditional medicinal plants in malaria-endemic regions. Previous studies on two chalcones, homobutein and 5-prenylbutein, present in E. abyssinica, have shown moderate antiplasmodial activity. Here, we describe results from experimental and computational investigations of four structurally related chalcones, butein, 2′,4′-dihydroxy-3,4-dimethoxychalcone (DHDM), homobutein and 5-prenylbutein to elucidate possible molecular mechanisms by which these compounds clear malaria parasites. The crystal structures of butein and DHDM show that butein engages in more hydrogen bonding and consequently, more intermolecular interactions than DHDM. Rotating ring-disk electrode (RRDE) voltammetry results show that butein has a higher antioxidant activity towards the superoxide radical anion compared to DHDM. Computational docking experiments were conducted to examine the inhibitory potential of all four compounds on falcipain-2, a cysteine protease that is involved in the degradation of hemoglobin in plasmodium-infected red blood cells of the host. Overall, this work suggests butein as a better antimalarial compound due to its structural features which allow it to have greater intermolecular interactions, higher antioxidant activity and to create a covalent complex at the active site of falcipain-2.

Antioxidant Properties of Thymoquinone, Thymohydroquinone and Black Cumin (Nigella sativa L.) Seed Oil: Scavenging of Superoxide Radical Studied Using Cyclic Voltammetry, DFT and Single Crystal X-ray Diffraction

“…Shorter single bonds and longer double bonds can be associated with ring aromatization, suggesting the unpaired electron of superoxide is donated to the quinone ring. This result has already been observed by us in related polyphenols scavenging superoxide [ 21 ]. The electron captured by the ring also has an effect on the C=O bond lengths as they become elongated by 0.03 Å.…”

Antioxidant properties of bee propolis and an important component, galangin, described by X-ray crystal structure, DFT-D and hydrodynamic voltammetry

“…Our previous investigations on superoxide scavenging by embelin [ 31 ] emodin [ 32 ], and chalcones [ 33 ] described an additional mode of sequestering superoxide, through the π-π interaction between superoxide radical and the polyphenol. This scavenging mechanism is suggested for galangin as well, since, as described later in RRDE results, galangin is experimentally found to be an excellent scavenger of superoxide, and additional options need to be considered.…”

Examining the Antioxidant and Superoxide Radical Scavenging Activity of Anise, (Pimpinella anisum L. Seeds), Esculetin, and 4-Methyl-Esculetin Using X-ray Diffraction, Hydrodynamic Voltammetry and DFT Methods

“…The electrochemical technique [ 24 ] developed in our laboratory is very useful to study the scavenging of superoxide by small organic molecules found in fruit and vegetables. We have used it to describe the behavior of flavonoids [ 24 , 29 , 30 ], chalcones [ 31 ], coumarins [ 12 ], and quinones [ 32 , 33 , 34 ]. We also investigated the scavenging capacity of several integral natural products along with phytochemicals contained in the same natural products.…”