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Colorectal cancer remains a significant cause of mortality worldwide. A spiro-acridine derivative, (E)-1′-((4-bromobenzylidene)amino)-5′-oxo-1′,5′-dihydro-10H-spiro[acridine-9,2′-pyrrole]-4′-carbonitrile (AMTAC-19), showed significant cytotoxicity in HCT-116 colorectal carcinoma cells (half maximal inhibitory concentration, IC50 = 10.35 ± 1.66 µM) and antioxidant effects after 48 h of treatment. In this study, Molegro Virtual Docker v.6.0.1 software was used to investigate the interactions between AMTAC-19 and the Extracellular Signal-Regulated Kinase 1 (ERK1), c-Jun N-terminal Kinase 1 (JNK1), and p38 Mitogen-Activated Protein Kinase α (p38α MAPK). In vitro assays were conducted in HCT-116 cells to evaluate the effect of AMTAC-19 on the modulation of these proteins’ activities using flow cytometry. Furthermore, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in the presence or absence of ERK1/2, JNK, and p38 MAPK inhibitors was used to evaluate the involvement of these enzymes in AMTAC-19 cytotoxicity. ROS production was assessed using the 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA) assay at various incubation times (30 min, 1 h, 6 h, 12 h, and 24 h), and the MTT assay using N-acetyl-L-cysteine (NAC) was performed. In silico results indicated that AMTAC-19 interacts with ERK1, JNK1, and p38α MAPK. Additionally, AMTAC-19 activated ERK1/2 and JNK1 in HCT-116 cells, and its cytotoxicity was significantly reduced in the presence of ERK1/2 and JNK inhibitors. AMTAC-19 also induced a significant increase in ROS production (30 min and 1 h), while NAC pretreatment reduced its cytotoxicity. These findings support AMTAC-19′s in vitro antitumor effect through ROS-dependent activation of ERK and JNK pathways.

Canthin‐6‐one alkaloids, which are present in plants of the genus Simaba, are natural compounds that are capable of acting as fluorescent probes. However, the chemical composition and fluorescent properties of most species of this genus have not been analyzed. The objective of this study was to characterize the fluorescent properties of an extract of S. bahiensis and identify the chemical entities responsible for these properties. In addition, the cell‐labeling properties of the fluorescent dye from A and of the isolated compounds were characterized by confocal fluorescence microscopy and flow cytometry. One quassinoid and three fluorescent alkaloids were isolated from S. bahiensis, all compounds were identified by using NMR spectroscopy and high‐resolution mass spectrometry. Staining experiments and HPLC‐FL analysis shown that canthin‐6‐one alkaloids are the main green fluorescent compounds in the analyzed dyes. All compounds evaluated showed a cytoplasmic marker with a residence time of 24 h. The present study is the first to describe the presence of canthin‐6‐one alkaloids in S. bahiensis, in addition to demonstrating promising cell‐labeling properties of fluorescent compounds from S. bahiensis with broad emission wavelengths. Natural talent: Fluorescent Simaba bahiensis extracts and their component fluorescent compounds act as fluorescent markers in HEP‐G2 cells. The cell‐labeling profile, characterized using confocal microscopy and flow cytometry, shows that extracted and pure compounds act on cytoplasm regions, and kinetic evaluation shows that labeling persists for 24 h.

Fifty 2-[(arylidene)amino]-4,5-cycloalkyl[b]thiophene-3-carbonitrile derivatives were screened for their in vitro antifungal activities against Candida krusei and Cryptococcus neoformans. Based on experimentally determined minimum inhibitory concentration (MIC) values, we conducted computer-aided drug design studies [molecular modelling, chemometric tools (CPCA, PCA, PLS) and QSAR-3D] that enable the prediction of three-dimensional structural characteristics that influence the antifungal activities of these derivatives. These predictions provide direction with regard to the syntheses of new derivatives with improved biological activities, which can be used as therapeutic alternatives for the treatment of fungal infections.

Lamiaceae is one of the largest families of angiosperms and is classified into 12 subfamilies that are composed of 295 genera and 7775 species. It presents a variety of secondary metabolites such as diterpenes that are commonly found in their species, and some of them are known to be chemotaxonomic markers. The aim of this work was to construct a database of diterpenes and to use it to perform a chemotaxonomic analysis among the subfamilies of Lamiaceae, using molecular descriptors and self-organizing maps (SOMs). The 4115 different diterpenes corresponding to 6386 botanical occurrences, which are distributed in eight subfamilies, 66 genera, 639 different species and 4880 geographical locations, were added to SistematX. Molecular descriptors of diterpenes and their respective botanical occurrences were used to generate the SOMs. In all obtained maps, a match rate higher than 80% was observed, demonstrating a separation of the Lamiaceae subfamilies, corroborating with the morphological and molecular data proposed by Li et al. Therefore, through this chemotaxonomic study, we can predict the localization of a diterpene in a subfamily and assist in the search for secondary metabolites with specific structural characteristics, such as compounds with potential biological activity.

Background: (-)-Fenchone is a naturally occurring monoterpene found in the essential oils of Foeniculum vulgare Mill., Thuja occidentalis L., and Peumus boldus Molina. Pharmacological studies have reported its antinociceptive, antimicrobial, anti-inflammatory, antidiarrheal, and antioxidant activities. Methods: The preventive antiulcer effects of (-)-Fenchone were assessed through oral pretreatment in cysteamine-induced duodenal lesion models. Gastric healing, the underlying mechanisms, and toxicity after repeated doses were evaluated using the acetic acid-induced gastric ulcer rat model with oral treatment administered for 14 days. Results: In the cysteamine-induced duodenal ulcer model, fenchone (37.5–300 mg/kg) significantly decreased the ulcer area and prevented lesion formation. In the acetic acid-induced ulcer model, fenchone (150 mg/kg) reduced (p < 0.001) ulcerative injury. These effects were associated with increased levels of reduced glutathione (GSH), superoxide dismutase (SOD), interleukin (IL)-10, and transforming growth factor-beta (TGF-β). Furthermore, treatment with (-)-Fenchone (150 mg/kg) significantly reduced (p < 0.001) malondialdehyde (MDA), myeloperoxidase (MPO), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and nuclear transcription factor kappa B (NF-κB). A 14-day oral toxicity investigation revealed no alterations in heart, liver, spleen, or kidney weight, nor in the biochemical and hematological parameters assessed. (-)-Fenchone protected animals from body weight loss while maintaining feed and water intake. Conclusion: (-)-Fenchone exhibits low toxicity, prevents duodenal ulcers, and enhances gastric healing activities. Antioxidant and immunomodulatory properties appear to be involved in its therapeutic effects.

Secondary metabolite production by plants is influenced by external environmental factors that can change depending on the seasons, which makes it important to know how the plant, through its metabolism, is able to adapt to these variations. Mentha x villosa and Plectranthus amboinicus present in their chemical composition polyphenols, and through previous studies, it has been seen that these two species present promising in vitro photoprotective activity. The aim of this study was to evaluate seasonal alterations in photoprotective and antioxidant activities and the influence of factors such as precipitation levels and sun radiation incidence. Thus, polyphenol quantification, cromatographics (HPLC-DAD) and multivariate (PCA) analyses of extracts of the two species through twelve months were done. It was observed that the best months for photoprotective and antioxidant activities were September for M. villosa and July for P. amboinicus (SPF = 14.79). It was possible to conclude that solar radiation more clearly influences the production of phenolics and the increase of SPF in M. villosa, in addition to favoring the antioxidant activity of the two species, while precipitation seems to have no influence.

Apocynaceae is a botanical family distributed mainly in tropical and subtropical regions of the world. In Brazil, they comprise about 90 genera and 850 species, inhabiting various types of vegetation. Within this large botanical family, the genus Hancornia is considered monotypic, with its only species Hancornia speciosa Gomes. Antihypertensive, antidiabetic, and antiviral activities are described for this species. Despite having been the target of some studies, knowledge of its chemical composition is still limited. In this study, the phenolics of H. speciosa leaves were analyzed using ultra-high performance liquid chromatography (UHPLC) coupled to Orbitrap high-resolution mass spectrometry (HRMS). As a result, 14 compounds were identified viz. protocatechuic acid, catechin, and quercetin, and another 14 were putatively identified viz. B- and C-type procyanidins, while just one compound remained unknown. From the identified compounds, 17 are reported for the first time viz. coumaroylquinic acid isomers and eriodyctiol. The results show that Hancornia speciosa can serve as source of valuable phenolics.

Cenostigma pluviosum var. peltophoroides, known as “sibipiruna,” is a plant rich in polyphenols used in traditional medicine for gastrointestinal disorders. The study aimed to investigate the chemical composition of the crude ethanolic extract of the stem bark (CEECP), evaluating its in vivo toxicity, genotoxicity, mutagenicity and anti-inflammatory activity. The plant material was macerated in 95% ethanol for 72 h, and the solvent was removed by rotary evaporation to obtain CEECP. Chemical characterization was performed by HPLC-ESI-MS/MS in negative mode. In vivo approaches were performed using male/female Swiss albino mice. Acute toxicity was assessed at a single high dose of 2000 mg/kg. Mutagenicity was investigated by the micronucleus test and genotoxicity by the comet assay, both at a dose of 2000 mg/kg. Anti-inflammatory activity was evaluated in carrageenan-induced paw edema and peritonitis models, at doses of 50, 100, and 200 mg/kg. HPLC-ESI-MS/MS analysis showed the presence of hydrolyzable tannins, phenolic acid heterosides, and biflavonoids. The safety profile of the CEECP was demonstrated for the first time, with no evidence of acute toxicity, mortality, mutagenicity, or genotoxicity at the tested doses. The extract significantly reduced paw edema in a dose-dependent manner at doses of 100 and 200 mg/kg, with inhibition rates of 65.78% and 73.12%, respectively, and also decreased leukocyte migration in the peritonitis model by 61.81% and 72.79% at the same doses. These findings indicate the CEECP as a source of pharmacologically relevant phytocompounds and, most notably, demonstrate its pronounced anti-inflammatory activity. Furthermore, the extract exhibited a favorable safety profile in the toxicological evaluations, highlighting the extract as a promising anti-inflammatory agent.

Calotropis procera, known as “Silk cotton”, stands out for the presence of various classes of bioactive compounds responsible for its ethnopharmacological properties. The study aimed to conduct a phytochemical investigation, evaluating the in vitro and in vivo toxicity together with the antinociceptive potential of an n-butanolic fraction (FB) from the leaves. The crude ethanolic extract (CEE) was obtained by maceration in ethanol for 72 h. It was then partitioned using a gradual solvent sequence. The FB was analyzed by HPLC-ESI-MS/MS in negative mode and 1H and 13C NMR. Toxicity was assessed by the erythrocyte hemolytic assay and acute oral toxicity test at a single dose of 300 mg·kg−1. The antinociceptive effect was assessed by the acetic acid-induced abdominal writhing test and the formalin test in mice at doses of 3.75, 7.5 and 15 mg·kg−1 per os. HPLC-ESI-MS/MS analysis identified flavonoids, phenolic acids, and the megastigmane roseoside, isolated for the first time in C. procera. The FB did not cause hemolytic effects or behavioral or physiological changes in mice. It showed an antinociceptive effect at all doses, reducing abdominal writhing by up to 91.46% and the licking time in phases 1 and 2 of the formalin test by up to 63.83% and 91.73%, respectively. In this study, it was possible to determine that an FB of a crude extract of C. procera leaves has antinociceptive activity, possibly associated with the phenolic compounds and roseoside found, with a lack of toxicity in vitro and in vivo, validating its ethnopharmacological use.

Fabaceae family is recognized as a prolific flavonoid producer, including some unusual flavonoid skeletons. Although classic flavonoids have well-established biological properties in the literature, these unusual compounds remain underinvestigated. Based on that, the current study sought to explore the chemistry and biological activity of rare flavonoids in Fabaceae with a review comprising their occurrence, extraction, isolation and pharmacological potential. Additionally, the use of LC-MS applied to the study of seven subclasses (aurones, biflavonoids, coumestans, homoisoflavonoids, neoflavonoids, pterocarpans, and rotenoids) is also discussed. The review was carried out by searching for specified uniterms on SciFinder and Web of Science, covering the last ten years. In addition, to assess ADMET and drug-like properties by in silico predictions, all the substances considered in this work were compiled and organized into a curated dataset. As a result, a total of 170 flavonoid structures were included, most of which were found in the roots and leaves. In addition, a wide range of biological activities were observed, such as cytotoxic, antiviral and anti-inflammatory. Despite advancements in the use of LC-MS for bioprospection, just a few reports dedicated to the study of these compounds were found. Regarding ADMET profiles, most subclasses showed favorable bioavailability characteristics, with biflavonoids being the main exception. Together, this review highlights the significance of unusual flavonoids from the Fabaceae family, demonstrating their remarkable chemical diversity and largely, but still, unexplored pharmacological potential. These findings encourage further investigations, particularly in the fields of natural products chemistry, medicinal chemistry, and pharmacology.