Indole alkaloids and synthetic indole derivatives are well known for their therapeutic importance. In fact, preclinical and clinical studies had already demonstrated several pharmacological activities for these compounds. Here, we overview the multifunctional potential of these molecules for the inhibition of enzymes related to neurodegenerative disease: acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidases A and B (MAO-A and MAO-B). A focus will be given on Psychotria L. genus, considering its reported central effects. Finally, three Psychotria alkaloids, namely desoxycordiofoline (61), bahienoside A (64) and bufotenine (65), along with the synthetic indole derivatives (5S)- 5-(1H-indol-3-ylmethyl)imidazolidine-2,4-dione (66), 5-(1H-indol-3-ylmethyl)-2-thioxoimidazolin-4-one (67), 5-(1Hindol- 3-ylmethyl)-3-methyl-2-thioxoimidazolidin-4-one (68), and methyl 2-(aminoN-(2-(4-methylcyclohex-3-enyl)propan- 2-yl)methanethioamino)-3-(1H-indol-3-yl)propanoate (69), were evaluated in vitro regarding their interactions with AChE, BChE, MAO-A and MAO-B. It was observed that 66 and 68 were able to inhibit MAO-A activity with IC₅₀ value of 8.23 and 0.07 μM. Molecular docking calculations were performed in order to understand the interactions between both ligands (66 and 68) and MAO-A. It was observed that the indole scaffold of both compounds bind into the MAO-A active site in the same orientation, establishing van der Waals contacts with lipophilic amino acids. Additionally, the hydantoin ring of 66 is able to interact by hydrogen bonds with two conserved water molecules in the MAO-A active site, while the methyl-thiohydantoin ring of 68 is within hydrogen bond distance from the hydrogen atom attached to the (N-5) of FAD cofactor. Taking together, our findings demonstrate that the indolyl-hydantoin and indolylmethyl-thiohydantoin rings might consists of good scaffolds for the development of new MAO-A inhibitors possessing neuroprotective properties.

Plant-derived products have played a fundamental role in the development of new therapeutic agents. This study aimed to analyze antimicrobial, antibiofilm, cytotoxicity and antiproliferative potentials of the extract and fractions from leaves of Himatanthus drasticus, a plant from the Apocynaceae family. After harvesting, H. drasticus leaves were macerated and a hydroalcoholic extract (HDHE) and fractions were prepared. Antimicrobial tests, such as agar-diffusion, Minimum Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) were carried out against several bacterial species. Staphylococcus aureus, Pseudomonas aeruginosa, Listeria monocytogenes and Klebsiella pneumoniae were inhibited by at least one extract or fraction in the agar-diffusion assay (inhibition halos from 12 mm to 30 mm). However, the lowest MIC value was found for HDHE against K. pneumoniae. In addition, HDHE and its fractions were able to inhibit biofilm formation at sub-inhibitory concentrations (780 µg/mL and 1.56 µg/mL). As the best activities were found for HDHE, we selected it for further assays. HDHE was able to increase ciprofloxacin (CIP) activity against K. pneumoniae, displaying synergistic (initial concentration CIP + HDHE: 2 µg/mL + 600 µg/mL and 2.5 µg/mL + 500 µg/mL) and additive effects (CIP + HDHE: 3 µg/mL + 400 µg/mL). This action seems to be associated with the alteration in bacterial membrane permeability induced by HDHE (as seen by propidium iodide labeling). This extract was non-toxic for red blood cell or human peripheral blood mononuclear cells (PBMCs). Additionally, it inhibited the lipopolysaccharide-induced proliferation of PBMCs. The following compounds were detected in HDHE using HPLC-ESI-MS analysis: plumieride, plumericin or isoplumericin, rutin, quercetin and derivatives, and chlorogenic acid. Based on these results we suggest that compounds from H. drasticus have antimicrobial and antibiofilm activities against K. pneumoniae and display low cytotoxicity and anti-proliferative action in PBMC stimulated with lipopolysaccharide.

Kielmeyera coriacea Mart., native to Brazilian Cerrado, is traditionally used in folk medicine. The MIC against bacteria and yeasts was determined for the ethanolic extracts of roots, outer bark, leaves, and fruits. A dereplication strategy via HPLC-ESI-HRMS/MS and GNPS was used to identify known compounds and highlight potential compounds responsible for the activities. The root extract exhibited the most promising activity against a range of bacteria and fungi. This extract was selected for further fractionation, yielding n-hexane, ethyl acetate, and hydroalcoholic fractions. These were evaluated against the same microbial strains. Subsequent chromatographic analysis and bioactivity tests identified two highly active subfractions from the n-hexane and hydroalcoholic fractions. Detailed analysis using standards and databases (GNPS and Scifinder) led to the annotation of three xanthones (kielcorin, and its hydroxy- and methoxy- derivatives), three glycosylated flavonoids, and two acylphoroglucinol derivatives (garcinielliptone D e A).