Dengue is a neglected disease responsible for 22,000 deaths each year in areas where it is endemic. To date, there is no clinically approved dengue vaccine or antiviral for human beings, even though there have been great efforts to accomplish these goals. Several approaches have been used in the search for dengue antivirals such as screening of compounds against dengue virus enzymes and structure-based computational discovery. During the last decades, researchers have turned their attention to nature, trying to identify compounds that can be used as dengue antivirals. Nature represents a vast reservoir of substances that can be explored with the aim of discovering new leads that can be either used directly as pharmaceuticals or can serve as lead structures that can be optimized towards the development of new antiviral agents against dengue. In this review we describe an assortment of natural products that have been reported as possessing dengue antiviral activity. The natural products are organized into classes of substances. When appropriate, structure-activity relationships are outlined. The biological assays used to assess antiviral activity are briefly described.

Bioinsecticides and transgenic plants, based on Bacillus thuringiensis (Bt) toxins are important when managing Anticarsia gemmatalis Hübner (Lepidoptera: Noctuidae), a soybean defoliator pest. The interaction of these toxins with the caterpillar’s midgut cells determines their efficacy as an insecticide. The objective was to evaluate the toxicity of B. thuringiensis, subsp. kurstaki strain HD-1 and cytopathological changes mediated by these bacterial toxins in the midgut of A. gemmatalis caterpillars. Insecticidal efficacy was determined by calculating lethal concentration values (LC₂₅, LC₅₀, LC₇₅, LC₉₀ and LC₉₉) in the laboratory. Midgut fragments from A. gemmatalis were extracted after bacterial ingestion and evaluated by light, transmission electron and confocal microscopy. The Bt median lethal concentrations showed toxicity [LC₅₀ = 0.46 (0.43–0.49) mg mL⁻¹] to fourth instar A. gemmatalis caterpillars after 108 hours. Bt induces severe cytotoxicity to A. gemmatalis midgut epithelial cells with increasing exposure over time, causing cellular disorganization, microvillus degeneration, cell fragmentation and protrusion, peritrophic membrane rupture, and cell vacuolization. The cell nuclei presented condensed chromatin and an increase in lysosome numbers. Apoptosis occurred in the midgut cells of caterpillars exposed to Bt. A regenerative response in A. gemmatalis caterpillars was observed 8 hours after exposure to Bt, however this response was not continuous. Toxins produced by Bt are harmful to A. gemmatalis at median concentration with structural damage and death of the midgut epithelial cells of this insect.

Context: In folk medicine, Schinus terebinthifolius Raddi (Anacardiaceae), has been used as a remedy for ulcers, respiratory problems, wounds, rheumatism, gout, diarrhea, skin ailments and arthritis, as well as to treat tumors and leprosy. Objective: To investigate the chemical composition and cytotoxicity of essential oil from leaves of S. terebinthifolius as well as the identification of active compounds from this oil. Material and methods: Essential oil from S. terebinthifolius leaves, obtained by hydrodistillation using a Clevenger-type apparatus, was characterized in terms of its chemical composition. Also, the crude oil was subjected to chromatographic separation procedures to afford an active fraction composed of α- and β-pinenes. These compounds, including hydrogenation (pinane) and epoxydation (α-pinene oxide) derivatives from α-pinene, were tested in vitro against murine melanoma cell line (B16F10-Nex2) and human melanoma (A2058), breast adenocarcinoma (MCF7), leukemia (human leukemia (HL-60) and cervical carcinoma (HeLa) cell lines. Results: Forty-nine constituents were identified in the oil (97.9% of the total), with germacrene D (23.7%), bicyclogermacrene (15.0%), β-pinene (9.1%) and β-longipinene (8.1%) as the main compounds. The crude essential oil showed cytotoxic effects in several cell lines, mainly on leukemia and human cervical carcinoma. Fractions composed mainly of α- and β-pinenes as well as those composed of individually pinenes showed effective activities against all tested cell lines. Aiming to determinate preliminary structure/activity relationships, α-pinene was subjected to epoxydation and hydrogenation procedures whose obtained α-pinene oxide showed an expressive depression in its cytotoxicity effect, similar as observed to pinane derivative. Discussion and conclusion: The obtained results indicated that the monoterpenes α- and β-pinenes could be responsible to the cytotoxic activity detected in the crude oil from leaves of S. terebinthifolius. In addition, it was possibly inferred that the presence of double bond in their structures, mainly at endocyclic position, is crucial to cytotoxic potential detected in these derivatives.