Fungal Biofilms as a Valuable Target for the Discovery of Natural Products That Cope with the Resistance of Medically Important Fungi-Latest Findings.

The development of new antifungal agents that target biofilms is an urgent need. Natural products, mainly from the plant kingdom, represent an invaluable source of these entities. The present review provides an update (2017-May 2021) on the available information on essential oils, propolis, extracts from plants, algae, lichens and microorganisms, compounds from different natural sources and nanosystems containing natural products with the capacity to in vitro or in vivo modulate fungal biofilms. The search yielded 42 articles; seven involved essential oils, two Brazilian propolis, six plant extracts and one of each, extracts from lichens and algae/cyanobacteria. Twenty articles deal with the antibiofilm effect of pure natural compounds, with 10 of them including studies of the mechanism of action and five dealing with natural compounds included in nanosystems. Thirty-seven manuscripts evaluated Candida spp. biofilms and two tested Fusarium and Cryptococcus spp. Only one manuscript involved Aspergillus fumigatus. From the data presented here, it is clear that the search of natural products with activity against fungal biofilms has been a highly active area of research in recent years. However, it also reveals the necessity of deepening the studies by (i) evaluating the effect of natural products on biofilms formed by the newly emerged and worrisome health-care associated fungi, C. auris, as well as on other non-albicans Candida spp., Cryptococcus sp. and filamentous fungi; (ii) elucidating the mechanisms of action of the most active natural products; (iii) increasing the in vivo testing.

Prospecting for cytotoxic and antiprotozoal 4-aryl-4H-chromenes and 10-aryldihydropyrano[2,3-f]chromenes.

Different studies reported that genetic predisposition or metabolic dysfunction are the risk factors for cancer. Infectious parasitic diseases were listed among factors that predispose to cancer. Because of the resemblance between the life cycle of cancer cells and some parasites, this study aimed to prepare pyran derivatives with cytotoxic and antiprotozoal potencies. Therefore, 7 chromenes, 10 pyranocoumarins, and an unexpected intermediate were obtained from a multi-reagent one-pot reaction. These compounds were evaluated for their cytotoxicity on sensitive and resistant leukemia cancer cells lines and against two protozoan parasites, namely Trypanosoma cruzi and Leishmania amazonensis amastigote. Promising cytotoxicity (IC50 values of less than 1 µM) was obtained for two of the synthetic products (12 and 15). Compound 12 induced apoptosis and cell cycle arrest in CCRF-CEM leukemia cells in G0/G1 while compound 15 and doxorubicin induced apoptosis and arrest in the S and G2/M phases. Ten of these products showed trypanocidal activity, while only five of them were weakly active on L. amazonensis. Three of the obtained pyrans showed significant cytotoxicity and antitrypanocidal activity, simultaneously. Nevertheless, all antiparasitic compounds revealed potency with low selectivity toward THP-1 cells used as host.

Cytotoxicity of an unprecedented brominated oleanolide and a new furoceramide from the Cameroonian spice, Echinops giganteus.

A preliminary study on Echinops giganteus (Asteraceae) showed that the methanolic extract has interesting cytotoxicities against a panel of cancer cell lines. From this extract, a lignan, a flavonoid and a polyacetylenic thiophene identified were three times less cytotoxic than the extract. In the search of the metabolites responsible for the bioactivity, a new harvested E. giganteus was subjected to a phytochemical study using chromatographic methods. In the course of the work, two new compounds: a brominated oleanolide (1) and a tetrahydrofurano-ceramide (2) were obtained along with ß-amyrin acetate (3), 2-(penta-1,3-diynyl)-5-(4-hydroxybut-1-ynyl)-thiophene (4), 2-(penta-1,3-diynyl)-5-(3,4-dihydroxybut-1-ynyl)-thiophene (5) and 4-hydroxy-2,6-di-(3',4'-dimethoxyphenyl)-3,7-dioxabicyclo-(3.3.0)octane (6). Their structures were determined on the basis of NMR spectroscopy and mass spectrometry data in conjunction with those reported in the literature. The cytotoxicity of 1, 2 and 5 was evaluated by employing resazurin assay against a panel of cancer cell lines with IC50 values in range 6.12 ± 0.46-46.96 ± 3.61 µM.