Targeted Anthocyanin Profiling of Fruits from Three Southern Highbush Blueberry Cultivars Propagated in Colombia.

The blueberry, a deciduous shrub in the Ericaceae family, is celebrated for its delightful flavor, sweetness, and abundance of anthocyanins and antioxidants, qualities that have garnered significant attention for their potential health benefits. Blueberries grown in diverse environments and exhibit varied anthocyanin profiles, often influenced by factors such as altitude and climate. Varietal groups worldwide have been bred and categorized based on their growth habits and specific cold requirements, particularly with southern highbush cultivars thriving in temperate climates, demonstrating tolerance to higher altitudes or cooler climates-a result of hybridizations involving various Vaccinium species. In the Colombian Andes, southern highbush blueberries thrive in unique high-altitude conditions, leading to exceptional quality due to the region's cool climate and specific soil characteristics. In this context, this study aimed to chemically characterize and differentiate three southern highbush blueberry cultivars (i.e., 'Biloxi,' 'Legacy' and 'Sharpblue') cultivated in a Colombian Andean plateau and compare them to three commercially available highbush blueberries. This comprehensive evaluation involved examining total phenols, flavonoids, anthocyanin content, and DPPH· free-radical scavenging capacity, as well as conducting anthocyanin-targeted profiling via HPLC-DAD-HRMS. Through supervised multivariate analyses such as sPLS-DA, this study delved into the pattern recognition of those anthocyanins that could potentially serve as markers for quality and cultivar-related chemical trait determination. These findings locate blueberry-derived anthocyanins in a metabolic context and afford some insights into southern highbush blueberry cultivar differentiation to be used for further purposes.

Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Therapeutics.

Natural products (NPs) from plants, fungi, animals, and microorganisms have historically played important roles in drug discovery [...].

Machine-Learning- and Structure-Based Virtual Screening for Selecting Cinnamic Acid Derivatives as Leishmania major DHFR-TS Inhibitors.

The critical enzyme dihydrofolate reductase-thymidylate synthase in Leishmania major (LmDHFR-TS) serves a dual-purpose role and is essential for DNA synthesis, a cornerstone of the parasite's reproductive processes. Consequently, the development of inhibitors against LmDHFR-TS is crucial for the creation of novel anti-Leishmania chemotherapies. In this study, we employed an in-house database containing 314 secondary metabolites derived from cinnamic acid that occurred in the Asteraceae family. We conducted a combined ligand/structure-based virtual screening to identify potential inhibitors against LmDHFR-TS. Through consensus analysis of both approaches, we identified three compounds, i.e., lithospermic acid (237), diarctigenin (306), and isolappaol A (308), that exhibited a high probability of being inhibitors according to both approaches and were consequently classified as promising hits. Subsequently, we expanded the binding mode examination of these compounds within the active site of the test enzyme through molecular dynamics simulations, revealing a high degree of structural stability and minimal fluctuations in its tertiary structure. The in silico predictions were then validated through in vitro assays to examine the inhibitory capacity of the top-ranked naturally occurring compounds against LmDHFR-TS recombinant protein. The test compounds effectively inhibited the enzyme with IC50 values ranging from 6.1 to 10.1 µM. In contrast, other common cinnamic acid derivatives (i.e., flavonoid glycosides) from the Asteraceae family, such as hesperidin, isovitexin 4'-O-glucoside, and rutin, exhibited low activity against this target. The selective index (SI) for all tested compounds was determined using HsDHFR with moderate inhibitory effect. Among these hits, lignans 306 and 308 demonstrated the highest selectivity, displaying superior SI values compared to methotrexate, the reference inhibitor of DHFR-TS. Therefore, continued research into the anti-leishmanial potential of these C6C3-hybrid butyrolactone lignans may offer a brighter outlook for combating this neglected tropical disease.

GC/MS-Based Fingerprinting Reveals Two Chemotypes in the Leaf Essential Oils from Magnolia grandiflora Trees within The Urban Forestry of a Colombian Andean Plateau.

Magnolia grandiflora is an aromatic plant widely distributed around the world. In Colombia, and more specifically in Bogotá, M. grandiflora has been introduced as part of urban forestry programs, and their specimens are therefore subjected to several environments. Nevertheless, there are no previous studies on the chemical composition of such plants. Hence, the characterization of the essential oil from 20 specimens of M. grandiflora from Bogotá, Colombia, by GC/MS was carried out here. Two different chemotypes were found. While one was characterized by monoterpenes α-pinene, ß-pinene, and limonene, the other contained mainly sesquiterpenes ß-elemene, bicyclogermacrene, and germacrene D. Multivariate statistical analyses confirmed their existence and helped to identify variations within and between chemotypes. Furthermore, differential expression of genes encoding the terpene synthases Mg25 and Mg17 could arguably be responsible for the characteristic compositions of both chemotypes, as suggested by rational biosynthetic analysis of the most contrasting metabolites.

Freshwater-Derived Streptomyces: Prospective Polyvinyl Chloride (PVC) Biodegraders.

Polyvinyl chloride (PVC) is widely used in industrial applications, such as construction and clothing, owing to its chemical, physical, and environmental resistance. Owing to the previous characteristics, PVC is the third most consumed plastic worldwide and, consequently, an increasing waste accumulation-related problem. The current study evaluated an in-house collection of 61 Actinobacteria strains for PVC resin biodegradation. Weight loss percentage was measured after the completion of incubation. Thermo-gravimetric analysis was subsequently performed using the PVC incubated with the three strains exhibiting the highest weight loss. GC-MS and ionic exchange chromatography analyses were also performed using the culture media supernatant of these three strains. After incubation, 14 strains had a PVC weight loss percentage higher than 50% in ISP-2 broth. These 14 strains were identified as Streptomyces strains. Strains 208, 250, and 290 showed the highest weight loss percentages (57.6-61.5% range). The thermal stability of PVC after bacterial exposure using these three strains was evaluated, and a modification of the representative degradation stages of nonincubated PVC was observed. Additionally, GC-MS analysis revealed the presence of aromatic compounds in the inoculated culture media, and ionic exchange chromatography showed chloride release in the supernatant. A mathematical relation between culture conditions and PVC weight loss was also found for strains 208 and 290, showing an accuracy up to 97.99%. These results highlight the potential of the freshwater-derived Streptomyces strains as candidates for the PVC biodegradation strategy and constitute the first approach to a waste management control scale-up process.

Composition and Antifungal Activity of the Alkaloidal Fraction of Lupinus mirabilis Leaves: A Biochemometrics-Based Exploration.

Lupinus plants are well-recognized due to their significant alkaloid content, which has made them the subject of several studies. However, the lack of chemical and biological information on the Colombian Lupinus species remains a fact. Therefore, the alkaloidal fractions from the leaves of L. mirabilis obtained by conventional solvent and ultrasound-assisted extraction (CSE and UAE, respectively) at different time frames were analyzed. Sparteine (2) was the main component in all cases; however, its relative abundance showed large variability, ranging from 64.7% to 80.6%. Minor constituents were also affected by the extraction conditions. In general, prolonged times gave a higher proportion of alkaloids under CSE, while only a slight decrease was observed under UAE. Both the method and extraction time appeared to equally affect the ratios of particular alkaloids, leading to variations in their effect on the mycelial growth of Fusarium oxysporum. Holistic analysis through multiple-covariate statistical methods as an approach to integrating chemical and bioactivity datasets allowed inferring the compounds most likely responsible for the changes in mycelial growth inhibition. 13α-Hydroxylupanine (12) might represent a promising compound to be included in further studies against this phytopathogen.

Identification of Anti-Proliferative Compounds from Genista monspessulana Seeds through Covariate-Based Integration of Chemical Fingerprints and Bioactivity Datasets.

Genista monspessulana (L.) L.A.S. Johnson (Fabaceae) is a Mediterranean plant introduced to South America and other regions for ornamental purposes. However, it is considered an invasive shrub due to its reproductive vigor in many areas. Unlike other Genista plants, G. monspessulana has few studies disclosing its biologically active components, particularly cytotoxic agents against cancer cells. Thus, as part of our research on anti-proliferative bioactives, a set of ethanolic seed extracts from ten accessions of G. monspessulana, collected in the Bogotá plateau, were evaluated against four cell lines: PC-3 (prostate adenocarcinoma), SiHa (cervical carcinoma), A549 (lung carcinoma), and L929 (normal mouse fibroblasts). Extracts were also analyzed through liquid chromatography coupled with mass spectrometry (LC/MS) to record chemical fingerprints and determine the composition and metabolite variability between accessions. Using multiple covariate statistics, chemical and bioactivity datasets were integrated to recognize patterns and identify bioactive compounds among studied extracts. G. monspessulana seed-derived extracts exhibited dose-dependent antiproliferative activity on PC-3 and SiHa cell lines (>500 µg/mL < IC50 < 26.3 µg/mL). Seven compounds (1−7) were inferred as the compounds most likely responsible for the observed anti-proliferative activity and subsequently isolated and identified by spectroscopic techniques. A tricyclic quinolizidine (1) and a pyranoisoflavone (2) were found to be the most active compounds, exhibiting selectivity against PC-3 cell lines (IC50 < 18.6 µM). These compounds were used as precursors to obtain a quinolizidine-pyranoisoflavone adduct via Betti reaction, improving the activity against PC-3 and comparable to curcumin as the positive control. Results indicated that this composition−activity associative approach is advantageous to finding those bioactive principles efficiently within active extracts. This correlative association can be employed in further studies focused on the targeted isolation of anti-proliferative compounds from Genista plants and accessions.

Quinolizidine-Based Variations and Antifungal Activity of Eight Lupinus Species Grown under Greenhouse Conditions.

Fusarium oxysporum is an aggressive phytopathogen that affects various plant species, resulting in extensive local and global economic losses. Therefore, the search for competent alternatives is a constant pursuit. Quinolizidine alkaloids (QA) are naturally occurring compounds with diverse biological activities. The structural diversity of quinolizidines is mainly contributed by species of the family Fabaceae, particularly the genus Lupinus. This quinolizidine-based chemo diversity can be explored to find antifungals and even mixtures to address concomitant effects on F. oxysporum. Thus, the antifungal activity of quinolizidine-rich extracts (QREs) from the leaves of eight greenhouse-propagated Lupinus species was evaluated to outline promising QA mixtures against F. oxysporum. Thirteen main compounds were identified and quantified using an external standard. Quantitative analysis revealed different contents per quinolizidine depending on the Lupinus plant, ranging from 0.003 to 32.8 mg/g fresh leaves. Bioautography showed that all extracts were active at the maximum concentration (5 µg/µL). They also exhibited >50% mycelium growth inhibition. All QREs were fungistatic except for the fungicidal QRE of L. polyphyllus Lindl. Angustifoline, matrine, 13α-hydroxylupanine, and 17-oxolupanine were ranked to act jointly against the phytopathogen. Our findings constitute reference information to better understand the antifungal activity of naturally afforded QA mixtures from these globally important plants.

Antiproliferative and Pro-Apoptotic Effects of a Phenolic-Rich Extract from Lycium barbarum Fruits on Human Papillomavirus (HPV) 16-Positive Head Cancer Cell Lines.

The in vitro antiproliferative activity of a phenolic-rich extract from Lycium barbarum fruits against head and neck HPV16 squamous cell carcinoma (OSCC) has been demonstrated, indicating for the first time that L. barbarum extract inhibits human papillomavirus (HPV) type 16 cell lines. Ethanol extract of L. barbarum was used for cell viability evaluation on SCC090, CAL27, and HGnF cell lines. After 24 and 48 h, the cell cycle effect of L. barbarum extract (at 1.0, 10, and 100 µg/mL) was measured via flow cytometry. In addition, the mRNA expression on E6/E7 and p53 via RT-PCR and the expression of p16, p53, Ki-67, and Bcl-2 via immunohistochemistry were also determined. Untreated cells, 20 µM cisplatin, and a Camellia sinensis-derived extract were used as negative and positive controls, respectively. We demonstrated that the studied L. barbarum extract resulted in G0/G1 arrest and S phase accumulation in SCC090 at 1.0 and 10 µg/mL. A reduction in mRNA levels of E6/E7 oncogenes (p < 0.05) with p53 overexpression was also observed through PCR, while immunohistochemical analyses indicated p16 overexpression (p > 0.05) and a decrease in p53 overexpression. The observed effects were associated with anticancer and immunomodulatory phenolics, such as flavonols/flavan-3-ols and tyramine-conjugated hydroxycinnamic acid amides, identified in the studied extract. These findings revealed that the phenolic-rich extract of L. barbarum fruits has promising properties to be considered further for developing new therapies against oral and oropharyngeal HPV lesions.

Selection of antileishmanial sesquiterpene lactones from SistematX database using a combined ligand-/structure-based virtual screening approach.

Leishmaniasis refers to a complex of diseases, caused by the intracellular parasitic protozoans belonging to the genus Leishmania. Among the three types of disease manifestations, the most severe type is visceral leishmaniasis, which is caused by Leishmania donovani, and is diagnosed in more than 20,000 cases annually, worldwide. Because the current therapeutic options for disease treatment are associated with several limitations, the identification of new potential leads/drugs remains necessary. In this study, a combined approach was used, based on two different virtual screening (VS) methods, which were designed to select promising antileishmanial agents from among the entire sesquiterpene lactone (SL) dataset registered in SistematX, a web interface for managing a secondary metabolite database that is accessible by multiple platforms on the Internet. Thus, a ChEMBL dataset, including 3159 and 1569 structures that were previously tested against L. donovani amastigotes and promastigotes in vitro, respectively, was used to develop two random forest models, which performed with greater than 74% accuracy in both the cross-validation and test sets. Subsequently, a ligand-based VS assay was performed against the 1306 SistematX-registered SLs. In parallel, the crystal structures of three L. donovani target proteins, N-myristoyltransferase, ornithine decarboxylase, and mitogen-activated protein kinase 3, and a homology model of pteridine reductase 1 were used to perform a structure-based VS, using molecular docking, of the entire SistematX SL dataset. The consensus analysis of these two VS approaches resulted in the normalization of probability scores and identified 13 promising, enzyme-targeting, antileishmanial SLs from SistematX that may act against L. donovani. A combined approach based on two different virtual screening methods (structure-based and ligand-based) was performed using an in-house dataset composed of 1306 sesquiterpene lactones to identify potential antileishmanial (Leishmania donovani) structures.

Machine learning models to select potential inhibitors of acetylcholinesterase activity from SistematX: a natural products database.

Alzheimer's disease is the most common form of dementia, representing 60-70% of dementia cases. The enzyme acetylcholinesterase (AChE) cleaves the ester bonds in acetylcholine and plays an important role in the termination of acetylcholine activity at cholinergic synapses in various regions of the nervous system. The inhibition of acetylcholinesterase is frequently used to treat Alzheimer's disease. In this study, a merged BindingDB and ChEMBL dataset containing molecules with reported half-maximal inhibitory concentration (IC50) values for AChE (7032 molecules) was used to build machine learning classification models for selecting potential AChE inhibitors from the SistematX dataset (8593 secondary metabolites). A total of seven fivefold models with accuracy above 80% after cross-validation were obtained using three types of molecular descriptors (VolSurf, DRAGON 5.0, and bit-based fingerprints). A total of 521 secondary metabolites (6.1%) were classified as active in this stage. Subsequently, virtual screening was performed, and 25 secondary metabolites were identified as potential inhibitors of AChE. Separately, the crystal structure of AChE in complex with (-)-galantamine was used to perform molecular docking calculations with the entire SistematX dataset. Consensus analysis of both methodologies was performed. Only eight structures achieved combined probability values above 0.5. Finally, two sesquiterpene lactones, structures 15 and 24, were predicted to be able to cross the blood-brain barrier, which was confirmed in the VolSurf+ quantitative model, revealing these two structures as the most promising secondary metabolites for AChE inhibition among the 8593 molecules tested. A consensus analysis of classification models and molecular docking calculations identified four potential inhibitors of acetylcholinesterase from the SistematX dataset (8593 structures).

Korean traditional foods as antiviral and respiratory disease prevention and treatments: A detailed review.

BACKGROUND: Korean traditional food (KTF), originated from ancestral agriculture and the nomadic traditions of the Korean peninsula and southern Manchuria, is based on healthy food that balances disease prevention and treatment. Fermented foods that include grains, herbs, fruits, and mushrooms are also an important practice in KTF, providing high levels of Lactobacilli, which confer relevant health benefits, including antiviral properties. Some of these probiotics may also protect against the Influenza virus through the modulation of innate immunity. SCOPE AND APPROACH: The emerging of the COVID-19 pandemic, in addition to other diseases of viral origin, and the problems associated with other respiratory disorders, highlight how essential is a healthy eating pattern to strengthen our immune system.Key Findings and Conclusions: The present review covers the information available on edible plants, herbs, mushrooms, and preparations used in KTF to outline their multiple medicinal effects (e.g., antidiabetic, chemopreventive, antioxidative, anti-inflammatory, antibacterial), emphasizing their role and effects on the immune system with an emphasis on modulating properties of the gut microbiota that further support strong respiratory immunity. Potential functional foods commonly used in Korean cuisine such as Kimchi (a mixture of fermented vegetables), Meju, Doenjang, Jeotgal, and Mekgeolli and fermented sauces, among others, are highlighted for their great potential to improve gut-lung immunity. The traditional Korean diet and dietary mechanisms that may target viruses ACE-2 receptors or affect any step of a virus infection pathway that can determine a patient's prognosis are also highlighted. The regular oral intake of bioactive ingredients used in Korean foods can offer protection for some viral diseases, through protective and immunomodulatory effects, as evidenced in pre-clinical and clinical studies.

Cliona varians-Derived Actinomycetes as Bioresources of Photoprotection-Related Bioactive End-Products.

Sunscreen and sunblock are crucial skincare products to prevent photoaging and photocarcinogenesis through the addition of chemical filters to absorb or block ultraviolet (UV) radiation. However, several sunscreen and sunblock ingredients, mostly UV filters, have been associated with human and environmental safety concerns. Therefore, the exploration and discovery of promising novel sources of efficient and safer compounds with photoprotection-related activities are currently required. Marine invertebrates, particularly their associated microbiota, are promising providers of specialized metabolites with valuable biotechnological applications. Nevertheless, despite Actinobacteria members being a well-known source of bioactive metabolites, their photoprotective potential has been poorly explored so far. Hence, a set of methanolic extracts obtained from Cliona varians-derived actinomycetes was screened regarding their antioxidant and UV-absorbing capacities (i.e., photoprotection-related activities). The active extract-producing strains were identified and classified within genera Streptomyces, Micrococcus, Gordonia, and Promicromonospora. This is the first report of the isolation of these microorganisms from C. varians (an ecologically important Caribbean coral reef-boring sponge). The in vitro cytotoxicity on dermal fibroblasts of oxybenzone and the selected active extracts revealed that oxybenzone exerted a cytotoxic effect, whereas no cytotoxic effect of test extracts was observed. Accordingly, the most active (SPFi > 5, radical scavenging > 50%) and nontoxic (cell viability > 75%) extracts were obtained from Streptomyces strains. Finally, LC-MS-based characterization suggested a broad chemical space within the test strains and agreed with the reported streptomycetes' chemodiversity. The respective metabolite profiling exposed a strain-specific metabolite occurrence, leading to the recognition of potential hits. These findings suggest that marine Streptomyces produce photoprotectants ought to be further explored in skincare applications.

Cactus: Chemical, nutraceutical composition and potential bio-pharmacological properties.

Cactus species are plants that grow in the arid and semiarid regions of the world. They have long fascinated the attention of the scientific community due to their unusual biology. Cactus species are used for a variety of purposes, such as food, fodder, ornamental, and as medicinal plants. In the last regard, they have been used in traditional medicine for eras by the ancient people to cure several diseases. Recent scientific investigations suggest that cactus materials may be used as a source of naturally-occurring products, such as mucilage, fiber, pigments, and antioxidants. For this reason, numerous species under this family are becoming endangered and extinct. This review provides an overview of the habitat, classification, phytochemistry, chemical constituents, extraction and isolation of bioactive compounds, nutritional and pharmacological potential with pre-clinical and clinical studies of different Cactus species. Furthermore, conservation strategies for the ornamental and endangered species have also been discussed.

Phytotherapy and food applications from Brassica genus.

Plants of the genus Brassica occupy the top place among vegetables in the world. This genus, which contains a group of six related species of a global economic significance, three of which are diploid: Brassica nigra (L.) K. Koch, Brassica oleracea L., and Brassica rapa L. and three are amphidiploid species: Brassica carinata A. Braun, Brassica juncea (L.) Czern., and Brassica napus L. These varieties are divided into oily, fodder, spice, and vegetable based on their morphological structure, chemical composition, and usefulness of plant organs. The present review provides information about habitat, phytochemical composition, and the bioactive potential of Brassica plants, mainly antioxidant, antimicrobial, anticancer activities, and clinical studies in human. Brassica vegetables are of great economic importance around the world. At present, Brassica plants are grown together with cereals and form the basis of global food supplies. They are distinguished by high nutritional properties from other vegetable plants, such as low fat and protein content and high value of vitamins, fibers along with minerals. In addition, they possess several phenolic compounds and have a unique type of compounds namely glucosinolates that differentiate these crops from other vegetables. These compounds are also responsible for numerous biological activities to the genus Brassica as described in this review.

Bioactivity and Biotechnological Overview of Naturally Occurring Compounds from the Dinoflagellate Family Symbiodiniaceae: A Systematic Review.

Marine invertebrates are a significant source of biologically active compounds. Recent studies have highlighted the role of microbiota associated with marine invertebrates in the production of bioactive compounds. Corals and sponges are the main marine invertebrates producing bioactive substances, and Symbiodiniaceae dinoflagellates are well-recognized endosymbionts with corals and sponges playing vital functions. The biological properties of Symbiodiniaceae-derived compounds have garnered attention in the past decades owing to their ecological implications and potentiality for bioprospecting initiatives. This study aims to systematically review studies on bioactivities and potential biotechnological applications of Symbiodiniaceae-derived compounds. The PRISMA guidelines were followed. Our study showed that anti-inflammatory and vasoconstrictive activities of Symbiodiniaceae-derived compounds have been the most investigated. However, very few studies have been published, with in vitro culturing of Symbiodiniaceae being the most significant challenge. Therefore, we surveyed for the metabolites reported so far, analyzed their chemodiversity, and discussed approaches to overcome culturing-related limitations.

Effect of Salt Stress on Growth and Metabolite Profiles of Cape Gooseberry (Physalis peruviana L.) along Three Growth Stages.

Colombia is the main producer of cape gooseberry (Physalis peruviana L.), a plant known for its various consumption practices and medicinal properties. This plant is generally grown in eroded soils and is considered moderately tolerant to unfavorable conditions, such as nutrient-poor soils or high salt concentrations. Most studies conducted on this plant focus on fruit production and composition because it is the target product, but a small number of studies have been conducted to describe the effect of abiotic stress, e.g., salt stress, on growth and biochemical responses. In order to better understand the mechanism of inherent tolerance of this plant facing salt stress, the present study was conducted to determine the metabolic and growth differences of P. peruviana plants at three different BBCH-based growth substages, varying salt conditions. Hence, plants were independently treated with two NaCl solutions, and growth parameters and LC-ESI-MS-derived semi-quantitative levels of metabolites were then measured and compared between salt treatments per growth substage. A 90 mM NaCl treatment caused the greatest effect on plants, provoking low growth and particular metabolite variations. The treatment discrimination-driving feature classification suggested that glycosylated flavonols increased under 30 mM NaCl at 209 substages, withanolides decreased under 90 mM NaCl at 603 and 703 substages, and up-regulation of a free flavonol at all selected stages can be considered a salt stress response. Findings locate such response into a metabolic context and afford some insights into the plant response associated with antioxidant compound up-regulation.

Identification of Kaurane-Type Diterpenes as Inhibitors of Leishmania Pteridine Reductase I.

The current treatments against Leishmania parasites present high toxicity and multiple side effects, which makes the control and elimination of leishmaniasis challenging. Natural products constitute an interesting and diverse chemical space for the identification of new antileishmanial drugs. To identify new drug options, an in-house database of 360 kauranes (tetracyclic diterpenes) was generated, and a combined ligand- and structure-based virtual screening (VS) approach was performed to select potential inhibitors of Leishmania major (Lm) pteridine reductase I (PTR1). The best-ranked kauranes were employed to verify the validity of the VS approach through LmPTR1 enzyme inhibition assay. The half-maximal inhibitory concentration (IC50) values of selected bioactive compounds were examined using the random forest (RF) model (i.e., 2ß-hydroxy-menth-6-en-5ß-yl ent-kaurenoate (135) and 3α-cinnamoyloxy-ent-kaur-16-en-19-oic acid (302)) were below 10 µM. A compound similar to 302, 3α-p-coumaroyloxy-ent-kaur-16-en-19-oic acid (302a), was also synthesized and showed the highest activity against LmPTR1. Finally, molecular docking calculations and molecular dynamics simulations were performed for the VS-selected, most-active kauranes within the active sites of PTR1 hybrid models, generated from three Leishmania species that are known to cause cutaneous leishmaniasis in the new world (i.e., L. braziliensis, L. panamensis, and L. amazonensis) to explore the targeting potential of these kauranes to other species-dependent variants of this enzyme.

Prostaglandins Isolated from the Octocoral Plexaura homomalla: In Silico and In Vitro Studies Against Different Enzymes of Cancer.

Prostaglandin A2-AcMe (1) and Prostaglandin A2 (2) were isolated from the octocoral Plexaura homomalla and three semisynthetic derivatives (3-5) were then obtained using a reduction protocol. All compounds were identified through one- and two-dimensional (1D and 2D) nuclear magnetic resonance (NMR) experiments. Additionally, evaluation of in vitro cytotoxic activity against the breast (MDA-MB-213) and lung (A549) cancer cell lines, in combination with enzymatic activity and molecular docking studies with the enzymes p38α-kinase, Src-kinase, and topoisomerase IIα, were carried out for compounds 1-5 in order to explore their potential as inhibitors of cancer-related molecular targets. Results showed that prostaglandin A2 (2) was the most potent compound with an IC50 of 16.46 and 25.20 µg/mL against MDA-MB-213 and A549 cell lines, respectively. In addition, this compound also inhibited p38α-kinase in 49% and Src-kinase in 59% at 2.5 µM, whereas topoisomerase IIα was inhibited in 64% at 10 µM. Enzymatic activity was found to be consistent with molecular docking simulations, since compound 2 also showed the lowest docking scores against the topoisomerase IIα and Src-kinase (-8.7 and -8.9 kcal/mol, respectively). Thus, molecular docking led to establish some insights into the predicted binding modes. Results suggest that prostaglandin 2 can be considered as a potential lead for development inhibitors against some enzymes present in cancer processes.

Solvent Free Three-Component Synthesis of 2,4,5-trisubstituted-1H-pyrrol-3-ol-type Compounds from L-tryptophan: DFT-B3LYP Calculations for the Reaction Mechanism and 3H-pyrrol-3-one↔1H-pyrrol-3-ol Tautomeric Equilibrium.

In this paper, we describe the solvent-free three-component synthesis of 2,4,5-trisubstituted-1H-pyrrol-3-ol-type compounds from L-tryptophan. The first step of the synthetic methodology involved the esterification of L-tryptophan in excellent yields (93-98%). Equimolar mixtures of alkyl 2-aminoesters, 1,3-dicarbonyl compounds, and potassium hydroxide (0.1 eq.) were heated under solvent-free conditions. The title compounds were obtained in moderate to good yields (45%-81%). Density functional theory using "Becke, 3-parameter, Lee-Yang-Parr" correlational functional (DFT-B3LYP) calculations were performed to understand the molecular stability of the synthesized compounds and the tautomeric equilibrium from 3H-pyrrol-3-one type intermediates to 1H-pyrrol-3-ol type aromatized rings.