Indole alkaloids: 2012 until now, highlighting the new chemical structures and biological activities.

Indole alkaloids have attracted attention because of their therapeutic properties, being anti-inflammatory, antinociceptive, antitumoural, antioxidant and antimicrobial. These compounds present a wide structural diversity, which is directly related to the genera of the producing plants, as well as the biological activities. Indole alkaloids have attracted attention over the last decade because of this combination of bioactivity and structural diversity. Therefore, this review presented recent (2012-2018) advances in alkaloids, focusing on new compounds, extraction methods and biological activities. As such, approximately 70 articles were identified, which showed 261 new compounds produced by plants of the families Apocynaceae, Rubiaceae, Annonaceae and Loganiaceae. In addition, different extraction methods were identified, and the structures of the new compounds were analysed. In addition to indole molecules, there were mono-indole-, di-indole-, vinblastine-, vimblastine-, gelsedine-, geissospermidine-, koumine-, geissospermidine-, iboga-, perakine-, corynanthe-, vincamine-, ajmaline-, aspidorpema-, strychnos-type, ß-carboline alkaloids and indole alkaloid glucosides. The reported biological activities are mainly anticancer, antibacterial, antimalarial, antifungal, antiparasitic, and antiviral, as well as anti-acetylcholinesterase and anti-butyrylcolinesterase properties. This review serves as a guide for those wishing to find the most recently identified alkaloid structures and their associated activities.

Extraction, isolation and in vitro evaluation of affinisine from Tabernaemontana catharinensis in human melanoma cells.

Plant compounds have been identified as new drug prototypes. In this line, this work aimed to isolate the indole alkaloid affinisine from Tabernaemontana catharinensis and test its antitumor activity. The alkaloid was isolated by silica gel open column chromatography from the ethanolic extract of the stem of T. catharinensis. Afterwards, this molecule was characterized by high-resolution mass spectrometry and nuclear magnetic resonance. In the next step, the cytotoxicity of the compound was tested against human melanoma cell lines (A375, WM1366 and SK-MEL-28) and a normal skin cell line (CCD-1059Sk) using a MTT (3-4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Cells treated with affinisine were evaluated by flow cytometry to analyze apoptosis and the induction of cell cycle arrest, to evaluate the dead mechanism. The metabolite was isolated in a 0.2% yield relative to the extract. Cytotoxic activity of the molecule was observed at 48 h, resulting in considerable growth inhibition rates in melanoma cells, especially in WM1366, which had the lowest IC50 (32.86 ± 2.54 µg/mL). The apoptosis rate was lower in A375 (56.66 and 86.71% with 57 and 65 µg/mL, respectively). Moreover, affinisine was able to significantly induce cell cycle arrest in different phases in the A375 and WM1366 cell lines. However, in SK-MEL-28 cells, cycle arrest was not observed. In summary, this compound significantly decreased the viability of tumor cells in a dose- and time-dependent manner for all evaluated lineages, reduced cell viability by the apoptosis mechanism and presented prominent activities of cell cycle arrest. In this way, the use of antineoplastic agents is among the most widely used therapeutic measures for the control and treatment of cancer. Affinisine is a promising prototype in the search for new drugs to treat cancer.

Bio-guided search of active indole alkaloids from Tabernaemontana catharinensis: Antitumour activity, toxicity in silico and molecular modelling studies.

Active plant metabolites have been used as prototype drugs. In this context, Tabernaemontana catharinensis (Apocynaceae) has been highlighted because of the presence of active indole alkaloids. Thus, this study aims the bio-guided search of T. catharinensis cytotoxic alkaloids. The chemical composition was identified by high-resolution mass spectrometry, and fractionation was performed by open column and preparative thin-layer chromatography, from plant stems. The enriched fractions were tested in vitro in tumour cells A375 (melanoma cell line) and A549 (adenocarcinomic human alveolar basal epithelial cells), and non-tumour Vero cells (African green monkey kidney epithelial cells). The alkaloids identified as active were submitted to in silico toxicity prediction by ADME-Tox and OSIRIS programs and, also, to molecular docking, using topoisomerase I (PDB ID: 1SC7) by iGEMDOCK. As a result, six sub-fractions were obtained, which were identified as containing 16-epi-affinine, 12-methoxy-n-methyl-voachalotine, affinisine, voachalotine, coronaridine hydroxyindoline and ibogamine, respectively. The affinisine-containing sub-fraction showed selective toxicity against A375, with an IC50 of 11.73 µg mL-1, and no cytotoxicity against normal cells (Vero). From the in silico toxicity test results, all indole alkaloid compounds had a low toxicity risk. The molecular docking data provided structural models and binding affinities of the plant's indole alkaloids and topoisomerase I. In summary, this bio-guided search revealed that the indole alkaloids from T. catharinensis display selective cytotoxicity in A375 tumour cells and toxicity in silico. Particularly, affinisine might be a chemotherapeutic for A375 melanoma cells.

Chemical constituents antioxidant and anticholinesterasic activity of Tabernaemontana catharinensis.

The present work aimed to analyze the alkaloid content of the ethanolic extract of Tabernaemontana catharinensis (Apocynaceae family) and its fractions as well as to evaluate their antioxidant and anticholinesterasic activities. The analyses of the ethanolic extract of T. catharinensis by mass spectrometry allowed identifying the presence of the alkaloids 16-epi-affinine, coronaridine-hydroxyindolenine, voachalotine, voacristine-hydroxyindolenine, and 12-methoxy-n-methyl-voachalotine, as well as an alkaloid with m/z 385.21 whose spectrum suggests a derivative of voacristine or voacangine. The extract and its alkaloid rich fractions showed antioxidant activity, especially those that contain the alkaloid m/z 385.21 or 16-epi-affinine with DPPH scavenging activity (IC50) between 37.18 and 74.69 µg/mL. Moreover, the extract and its fractions exhibited anticholinesterasic activity, particularly the fractions characterized by the presence of 12-methoxy-n-methyl-voachalotine, with IC50 = 2.1 to 2.5 µg/mL. Fractions with 16-epi-affinine combined good antioxidant (IC50 = 65.59 to 74.69 µg/mL) and anticholinesterasic (IC50 = 7.7 to 8.3 µg/mL) activities, representing an option for further studies aimed at treating neurodegenerative diseases.

Antioxidant Effect of Lippia alba (Miller) N. E. Brown.

Lippia alba is a shrub found in all regions of Brazil and other countries in South and Central America. L. alba exhibits variability among its different accessions, showing differences in morphology and in the composition of its essential oil. This study evaluated the phenolic profiles and the antioxidant activities of seven different accessions of L. alba. The seven accessions of L. alba studied exhibited an important phenolic content, and all accessions demonstrated antioxidant activity with different efficacies. The main flavonoids in all accessions were apigenin, luteolin, naringin and rutin. The Santa Vitória do Palmar accession exhibited higher naringin and total phenolic content. This extract was able to reduce hydrogen peroxide-induced oxidative damage in tissue homogenates of cerebellum, cerebral cortex, hippocampus and liver of Wistar rats.

Genus Mikania: chemical composition and phytotherapeutical activity

The genus Mikania ranks high in the list of best-selling natural products in the world. Its main distribution is in South America, but some species are found in Asia, North America and Africa. It is used for treating fever, rheumatism, colds and respiratory diseases, as well as snake bites and scorpion stings, due to its broad spectrum of action. There are approximately 430 species of this genus and only 12% have been studied, highlighting their chemical and pharmacological diversity. The main chemical groups are: coumarins and derivatives, sesquiterpenes, sesquiterpenes lactones, diterpenes, phytosterols/terpenoids and flavonoids. This review aims to supply useful references for scientists interested in natural products and the search for new compounds, from over the 300 already described for the genus.