Background: The indiscriminate use of antibiotics brings an alarming reality: in 2050, bacterial resistance could be the main cause of death in the world, resulting in the death of 10 million people, according to the World Health Organization (WHO). In this sense, to combat bacterial resistance, several natural substances, including chalcones, have been described in relation to antibacterial, representing a potential tool for the discovery of new antibacterial drugs. Objective: The objective of this study is to perform a bibliographic survey and discuss the main contributions in the literature about the antibacterial potential of chalcones in the last 5 years. Methods: A search was carried out in the main repositories, for which the publications of the last 5 years were investigated and discussed. Unprecedented in this review, in addition to the bibliographic survey, molecular docking studies were carried out to exemplify the applicability of using one of the molecular targets for the design of new entities with antibacterial activity. Results: In the last 5 years, antibacterial activities were reported for several types of chalcones, for which activities were observed for both gram-positive and gram-negative bacteria with high potency, including MIC values in the nanomolar range. Molecular docking simulations demonstrated important intermolecular interactions between chalcones and residues from the enzymatic cavity of the enzyme DNA gyrase, one of the validated molecular targets in the development of new antibacterial agents. Conclusion: The data presented demonstrate the potential of using chalcones in drug development programs with antibacterial properties, which may be useful to combat resistance, a worldwide public health problem.

Carajurin is the main constituent of Arrabidaea chica species with reported anti-Leishmania activity. However, its mechanism of action has not been described. This study investigated the mechanisms of action of carajurin against promastigote forms of Leishmania amazonensis. Carajurin was effective against promastigotes with IC₅₀ of 7.96 ± 1.23 μg.mL⁻¹ (26.4 µM), and the cytotoxic concentration for peritoneal macrophages was 258.2 ± 1.20 μg.mL⁻¹ (856.9 µM) after 24 h of treatment. Ultrastructural evaluation highlighted pronounced swelling of the kinetoplast with loss of electron-density in L. amazonensis promastigotes induced by carajurin treatment. It was observed that carajurin leads to a decrease in the mitochondrial membrane potential (p = 0.0286), an increase in reactive oxygen species production (p = 0.0286), and cell death by late apoptosis (p = 0.0095) in parasites. Pretreatment with the antioxidant NAC prevented ROS production and significantly reduced carajurin-induced cell death. The electrochemical and density functional theory (DFT) data contributed to support the molecular mechanism of action of carajurin associated with the ROS generation, for which it is possible to observe a correlation between the LUMO energy and the electroactivity of carajurin in the presence of molecular oxygen. All these results suggest that carajurin targets the mitochondria in L. amazonensis. In addition, when assessed for its drug-likeness, carajurin follows Lipinski’’s rule of five, and the Ghose, Veber, Egan, and Muegge criteria.

Leishmaniasis is a group of neglected tropical diseases whose treatment with antimonials bears limitations and has changed little in over 80 years. Medicinal plants have been evaluated as a therapeutic alternative for leishmaniasis. Arrabidaea chica is popularly used as a wound healing and antiparasitic agent, especially as leishmanicidal agent. This study examined the leishmanicidal activity of a crude extract (ACCE), an anthocyanidin-rich fraction (ACAF), and three isolated anthocyanidins from A. chica: carajurin, 3'-hydroxy-carajurone, and carajurone. We evaluated the antileishmanial activity against promastigote and intracellular amastigote forms of Leishmania amazonensis and determined cytotoxicity in BALB/c peritoneal macrophages, as well as nitrite quantification, using the Griess method. Molecular docking was carried out to evaluate interactions of carajurin at the nitric oxide synthase enzyme. All compounds were active against promastigotes after 72 h, with IC₅₀ values of 101.5 ± 0.06 μg/mL for ACCE and 4.976 ± 1.09 μg/mL for ACAF. Anthocyanidins carajurin, 3'-hydroxy-carajurone, and carajurone had IC₅₀ values of 3.66 ± 1.16, 22.70 ± 1.20, and 28.28 ± 0.07 μg/mL, respectively. The cytotoxicity assay after 72 h showed results ranging from 9.640 to 66.74 µg/mL for anthocyanidins. ACAF and carajurin showed selectivity against intracellular amastigote forms (SI> 10), with low cytotoxicity within 24 h, a statistically significant reduction in all infection parameters, and induced nitrite production. Molecular docking studies were developed to understand a possible mechanism of activation of the nitric oxide synthase enzyme, which leads to an increase in the production of nitric oxide observed in the other experiments reported. These results encourage us to suggest carajurin as a biological marker of A. chica.

Background: Alzheimer’s disease (AD) is one of the most prevalent types of dementia, affecting millions of older people worldwide. AD is stimulating efforts to develop novel molecules targeting its main features associated with a decrease in acetylcholine levels, an increase in oxidative stress and depositions of amyloid-β (Aβ) and tau protein. In this regard, selenium-containing compounds have been demonstrated as potential multi-targeted compounds in the treatment of AD. These compounds are known for their antioxidant and anticholinesterase properties, causing a decrease in Aβ aggregation.Objective: In this review, we approach structure-activity relationships of each compound, associating the decrease of ROS activity, an increase of tau-like activity and inhibition of AChE with a decrease in the self-aggregation of Aβ.Methods: We also verify that the molecular descriptors apol, nHBAcc and MlogP may be related to optimized pharmacokinetic properties for anti-AD drugs.Results: In our analysis, few selenium-derived compounds presented similar molecular features to FDA-approved drugs.Conclusion: We suggest that unknown selenium-derived molecules with apol, nHBAcc and MlogP like FDA-approved drugs may be better successes with optimized pharmacokinetic properties in future studies in AD.

The synthesis and antioxidant, antinociceptive and antiedematogenic activities of sulfonamides derived from carvacrol—a druglike natural product—are reported. The compounds showed promising antioxidant activity, and sulfonamide derived from morpholine (S1) demonstrated excellent antinociceptive and antiedematogenic activities, with no sedation or motor impairment. The mechanism that underlies the carvacrol and derived sulfonamides’ relieving effects on pain has not yet been fully elucidated, however, this study shows that the antinociceptive activity can be partially mediated by the antagonism of glutamatergic signaling. Compound S1 presented promising efficacy and was predicted to have an appropriate medicinal chemistry profile. Thus, derivative S1 is an interesting starting point for the design of new leads for the treatment of pain and associated inflammation and prooxidative conditions.

The present work reports the isolation and biological evaluation of three dimeric xanthones from Paecilomyces sp. EJC01.1 isolated as endophytic from Schnella splendens, a typical plant of the Amazon. The compounds phomoxanthone A (1), phomoxanthone B (2) and dicerandrol B (3) were isolated by chromatographic procedures and identified by spectroscopic methods of 1D and 2D NMR and MS. The extracts and compound 1 showed antimicrobial activities against Bacillus subtilis, Escherichia coli, Staphylococcus aureus, Salmonella typhimurium and Pseudomonas aeruginosa. The compound phomoxanthone A (1) showed greater inhibitory activity against B. subtilis (MIC of 7.81 µg mL⁻¹); in addition, it also pronounced inhibitory effect against promastigote forms of Leishmania amazonensis (IC₅₀ of 16.38 ± 1.079 µg mL⁻¹) and epimastigote forms Trypanosoma cruzi (IC₅₀ of 28.61 ± 1.071 µg mL⁻¹). To provide more information about the antibacterial activity of compound 1, an unprecedented molecular docking study was performed using S-ribosyl-homocysteine lyase (LuxS) (PDB ID 2FQO), which showed a possible interaction of phomoxanthone A with two of the residues (His58 and Cys126) that are fundamental for the catalysis mechanism in B. subtilis, which may be associated with the higher activity, when compared to other bacteria, observed in experimental studies. Additionally, quantum studies (DFT) were performed, for which a low gap value (5.982 eV) was observed, which corroborates the reactivity of phomoxanthone A. Thus, phomoxanthone A can be a good agent against pathogenic bacteria.