Chalcone Derivatives as Antibacterial Agents: An Updated Overview.

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. METHOD: 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.

Witches, potions, and metabolites: an overview from a medicinal perspective.

Witches were popularly imagined as older women (above middle age), with large warty noses, whose clothes were shabby and used pointy hats. They are usually associated with a cauldron and the presence of a black cat that accompany them in this imagery projection. The fact is that, historically, many women have suffered countless physical and emotional acts of violence, for which different analysis can be made from the perspective of the Human Sciences. Of the historical narratives that deal with this violence, the Salem witch trials stand out as the biggest witch hunt in history, where a series of hearings and trials of people accused of witchcraft took place in colonial Massachusetts, between February 1693 and May of 1694, episodes in which more than two hundred people were accused of practices of heresy. However, it is necessary to recognize that many of these women considered witches were, in fact, profound connoisseurs of plant species with biological properties, even though there was not precise information about the active compounds of these plants. With the development of characterization techniques for organic compounds, like spectrometric and spectroscopic analyses, most of the metabolites present in the "potions" had their structures elucidated, allowing a more appropriate knowledge of the possible metabolic pathways. In this article, we report a study of the structure-activity relationships for two of the most famous potions in history: the sleep potion and the love potion, with the aim of presenting new discussions within the scope of medicinal chemistry that can contribute to the process of science diffusion.

Novel trypanocidal thiophen-chalcone cruzain inhibitors: structure- and ligand-based studies.

Background: Chagas disease is a neglected tropical disease that affects millions of people worldwide and for which no effective treatment is available. Materials & methods: 17 chalcones were synthesized, for which the inhibition of cruzain and trypanocidal activity were investigated. Results: Chalcone C8 showed the highest cruzain inhibitory (IC50 = 0.536 µm) and trypanocidal activity (IC50 = 0.990 µm). Molecular docking studies showed interactions involving Asp161 and the thiophen group interacting with the S2 subsite. Furthermore, quantitative structure-activity relationship (q2 = 0.786; r2 = 0.953) and density functional theory studies were carried out, and a correlation between the lowest unoccupied molecular orbital surface and trypanocidal activity was observed. Conclusion: These results demonstrate that these chalcones are worthwhile hits to be further optimized in Chagas disease drug discovery programs.

In vitro evidence that the anti-inflammatory effect of synthetic cinnamate-derived dienes is directly linked to a macrophage repolarization.

The inflammatory process is a mammalian physiological reaction against infectious agents or injuries. Among the cells involved, the macrophages have a highlighted role during this process. Depending on the inflammatory context, they can polarize into pro- or anti-inflammatory profiles (M1 and M2). In this context, compounds derived from cinnamic acid have demonstrated strong evidence of anti-inflammatory activity; however, the mechanism responsible for this effect remains unclear. In this study, we investigated the anti-inflammatory activity of five cinnamate-derived dienes of synthetic origin. The compounds that did not demonstrate significant cytotoxicity were tested to assess anti-inflammatory activity (NOx ) in RAW 264.7 cells stimulated with LPS. Then, the selected compound (diene 1) was evaluated as to its ability to inhibit the secretion of pro-inflammatory cytokines (IL-1ß, TNF-α, INF-γ, MCP-1, and IL-6) and increase the production of anti-inflammatory cytokines (IL-13, IL-4, and IL-10). Finally, diene 1 was able to reduce the expression of TLR4 and increase the phagocytic activity of the macrophages. Gathering these results together, we conclude that diene 1 showed an important anti-inflammatory effect, and this effect is linked to its immunomodulatory characteristic. Since the M1 markers were reduced at the same time, M2 markers were increased by the treatment of the macrophages with diene 1.

Molecular Docking and Quantum Studies of Lawsone Dimers Derivatives: New Investigation of Antioxidant Behavior and Antifungal Activity.

BACKGROUND: In general, fungal species are characterized by their opportunistic character and can trigger various infections in immunocompromised hosts. The emergence of infections associated with high mortality rates is due to the resistance mechanisms that these species develop. METHODS: This phenomenon of resistance denotes the need for the development of new and effective therapeutic approaches. In this paper, we report the investigation of the antioxidant and antifungal behavior of dimeric naphthoquinones derived from lawsone whose antimicrobial and antioxidant potential has been reported in the literature. RESULTS: Seven fungal strains were tested, and the antioxidant potential was tested using the combination of the methodologies: reducing power, total antioxidant capacity and cyclic voltammetry. Molecular docking studies (PDB ID 5V5Z and 1EA1) were conducted which allowed the derivation of structureactivity relationships (SAR). Compound 1-i, derived from 3-methylfuran-2-carbaldehyde showed the highest antifungal potential with an emphasis on the inhibition of Candida albicans species (MIC = 0.5 µg/mL) and the highest antioxidant potential. CONCLUSION: A combination of molecular modeling data and in vitro assays can help to find new solutions to this major public health problem.