Green synthesis of ethyl cinnamates under microwave irradiation: photophysical properties, cytotoxicity, and cell bioimaging.

A simple and green method for the synthesis of six ethyl cinnamates was performed via Horner-Wadsworth-Emmons reaction under microwave irradiation. The photoluminescent properties of all compounds in ethyl acetate solutions were evaluated demonstrating that all compounds exhibit fluorescence. Five compounds exhibited blue emissions in the 369-442 nm range, and another compound exhibited blue-green emission at 504 nm. This last compound showed the largest Stokes shift (134 nm), and the highest quantum yield (17.8%). Two compounds showed extinction coefficient values (ε) higher than 30 000 M-1 cm-1, which are appropriate for cell bioimaging applications. In this sense, cytotoxicity assays were performed using Vero cells at different concentrations; the results showed that these compounds were not cytotoxic at the highest concentration tested (20 µg mL-1). Finally, the analysis by fluorescence microscopy for localization and cellular staining using Vero cells demonstrated that the compounds stained the cytoplasm and the nuclei in a selective way.

Formulation and optimization of polymeric nanoparticles loaded with riolozatrione: a promising nanoformulation with potential antiherpetic activity.

Riolozatrione (RZ) is a diterpenoid compound isolated from a dichloromethane extract of the Jatropha dioica root. This compound has been shown to possess moderate antiherpetic activity in vitro. However, because of the poor solubility of this compound in aqueous vehicles, generating a stable formulation for potential use in the treatment of infection is challenging. The aim of this work was to optimize and physio-chemically characterize Eudragit® L100-55-based polymeric nanoparticles (NPs) loaded with RZ (NPR) for in vitro antiherpetic application. The NPs formulation was initially optimized using the dichloromethane extract of J. dioica, the major component of which was RZ. The optimized NPR formulation was stable, with a size of 263 nm, polydispersity index < 0.2, the zeta potential of -37 mV, and RZ encapsulation efficiency of 89 %. The NPR showed sustained release of RZ for 48 h with release percentages of 95 and 97 % at neutral and slightly acidic pH, respectively. Regarding in vitro antiherpetic activity, the optimized NPR showed a selectivity index for HSV-1 of ≈16 and for HSV-2 of 13.

Towards an Eco-Friendly Coffee Rust Control: Compilation of Natural Alternatives from a Nutritional and Antifungal Perspective.

Hemileia vastatrix (HV) is the pathogen responsible for the coffee leaf rust (CLR) disease that has spread globally. CLR causes losses of up to a billion dollars annually and affects all types of crops regardless of their production regime (organic or inorganic). Additionally, smallholders produce approximately 80% of coffee in developing countries. The condition causes losses of up to a billion dollars annually. It affects all types of crops regardless of their production regime (organic or inorganic). Approximately 80% of coffee is produced by smallholders in developing countries. Until the 90s, shaded-production systems and native varieties were encouraged; however, the rapid spread of CLR has forced farmers to migrate towards inorganic schemes, mainly due to a lack of knowledge about natural alternatives to pesticides that can be implemented to control HV. Therefore, the purpose of this article is to compile the currently existing options, emphasizing two key factors that guarantee efficient rust control: selective fungicidal activity against HV and the nutrition of coffee crops. Thus, by comprehending how these natural compounds (such as plant, bacteria, fungi, animals, or algae metabolites) impact coffee rust proliferation. Furthermore, since a various range of biochar effects contributes to the control of foliar fungal pathogens through modification of root exudates, soil properties, and nutrient availability, which influence the growth of antagonist microorganisms, we present a review of the pathogen-suppressive effects of biochar, and new control strategies suitable for organic schemes can be developed.

Active Flavonoids from Colubrina greggii var. greggii S. Watson against Clinical Isolates of Candida spp.

Candida albicans is the most commonly implicated agent in invasive human fungal infections. The disease could be presented as minimal symptomatic candidemia or can be fulminant sepsis. Candidemia is associated with a high rate of mortality and high healthcare and hospitalization costs. The surveillance programs have reported the distribution of other Candida species reflecting the trends and antifungal susceptibilities. Previous studies have demonstrated that C. glabrata more frequently presents fluconazole-resistant strains. Extracts from Mexican plants have been reported with activity against pulmonary mycosis, among them Colubrina greggii. In the present study, extracts from the aerial parts (leaves, flowers, and fruits) of this plant were evaluated against clinical isolates of several species of Candida (C. albicans, C. glabrata, C. parapsilosis, C. krusei, and C. tropicalis) by the broth microdilution assay. Through bioassay-guided fractionation, three antifungal glycosylated flavonoids were isolated and characterized. The isolated compounds showed antifungal activity only against C. glabrata resistant to fluconazole, and were non-toxic toward brine shrimp lethality bioassay and in vitro Vero cell line assay. The ethyl acetate and butanol extracts, as well as the fractions containing the mixture of flavonoids, were more active against Candida spp.

Nanocarriers as Administration Systems of Natural Products.

Natural products are an important source of bioactive molecules. However, the development of biological applications based on these compounds is hindered by intrinsic problems in their solubility, volatility, degradation, and bioavailability. Nanocarriers as drug administration systems promise to overcome these limitations by providing controlled and directed delivery. This review aims to present 1) the most frequently used nanocarriers as natural product administration systems, based on the progress of controlled and directed release, and 2) the challenges associated with the use of nanocarriers as therapeutic agents.

Effect of the nO → π*C═O Interaction on the Conformational Preference of 1,3-Diketones: A Case Study of Riolozatrione Derivatives.

The cyclopropane ring-opening reaction of riolozatrione, a natural product obtained from Jatropha dioica, afforded a 2,2-disubstituted 1,3-cyclohexandione displaying an alkyl methyl ether group at position 5. The conformational analysis of this product showed a high preference for the trans-diaxial conformation in both solution and solid state. Such conformation was possible from the noncovalent intramolecular nX → π*C═O interactions (X = an element having an unshared electron pair), allowing the determination of the interaction energies. Since the nX → π*C═O interactions can be regarded as additive, the energy values ranged from 4.52 to 6.51 kcal mol-1 for each carbonyl group with a strong dependency on the interatomic distances. The rigorous analysis of the electron density in the topological theory of atoms in molecules framework clearly shows that the origin of O-C═O interactions are through the nO → π*C═O electron transfer mechanism. Such interactions are slightly weaker than a canonical hydrogen bond but seemingly stronger than a van der Waals interaction. This interaction must be considered as a stereoelectronic effect due the electronic transfer between the interacting groups, which are limited by their relative stereochemistry and can be represented by a bond-no bond interaction, causing the pyramidalization of the carbonyl, which is the charge acceptor group.

Molecular docking, SAR analysis and biophysical approaches in the study of the antibacterial activity of ceramides isolated from Cissus incisa.

The developing of antibacterial resistance is becoming in crisis. In this sense, natural products play a fundamental role in the discovery of antibacterial agents with diverse mechanisms of action. Phytochemical investigation of Cissus incisa leaves led to isolation and characterization of the ceramides mixture (1): (8E)-2-(tritriacont-9-enoyl amino)-1,3,4-octadecanetriol-8-ene (1-I); (8E)-2-(2',3'-dihydroxyoctacosanoyl amino)-1,3,4-octadecanetriol-8-ene (1-II); (8E)-2-(2'-hydroxyheptacosanoyl amino)-1,3,4-octadecanetriol-8-ene (1-III); and (8E)-2-(-2'-hydroxynonacosanoyl amino)-1,3,4-octadecanetriol-8-ene (1-IV). Until now, this is the first report of the ceramides (1-I), (1-II), and (1-IV). The structures were elucidated using NMR and mass spectrometry analyses. Antibacterial activity of ceramides (1) and acetylated derivates (2) was evaluated against nine multidrug-resistant bacteria by Microdilution method. (1) showed the best results against Gram-negatives, mainly against carbapenems-resistant Acinetobacter baumannii with MIC = 50 µg/mL. Structure-activity analysis and molecular docking revealed interactions between plant ceramides with membrane proteins, and enzymes associated with biological membranes of Gram-negative bacteria, through hydrogen bonding of functional groups. Vesicular contents release assay showed the capacity of (1) to disturb membrane permeability detected by an increase of fluorescence probe over time. The membrane disruption is not caused for ceramides lytic action on cell membranes, according in vitro hemolyticactivity results. Combining SAR analysis, bioinformatics and biophysical techniques, and also experimental tests, it was possible to explain the antibacterial action of these natural ceramides.

Antibacterial and cytotoxic activities of new sphingolipids and other constituents isolated from Cissus incisa leaves.

Cissus incisa is used in traditional Mexican medicine to treat certain ailments, infectious or cancerous diseases. Excepting for our previous research, this species had no scientific reports validating its traditional use. In this study, we evaluated the antibacterial and cytotoxic properties of the sphingolipids and others phytocompounds isolated from C. incisa leaves to increase the scientific knowledge of the Mexican flora. The antibacterial activity was evaluated against Gram-positive and Gram-negative bacteria by the Microdilution method. Meanwhile, the cytotoxic potential was determined on six human cancer cells: PC3, Hep3B, HepG2, MCF7, A549, and HeLa; using an aqueous solution cell proliferation assay kit. A cell line of immortalized human hepatocytes (IHH) was included as a control of non-cancerous cells. Selectivity index (SI) was determined only against the hepatocellular carcinoma cell lines. The phytochemical investigation of C. incisa leaves resulted in the isolation and characterization of five compounds: 2-(2'-hydroxydecanoyl amino)-1,3,4-hexadecanotriol-8-ene (1), 2,3-dihydroxypropyl tetracosanoate (2), ß-sitosterol-D-glucopyranoside (3), α-amyrin-3-O-ß-D-glucopyranoside (4), and a mixture of cerebrosides (5). Until now, this is the first report of the sphingolipids (1), (5-IV) and (5-V). Only the compound (4) and cerebrosides (5) exhibited antibacterial activity reaching a MIC value of 100 µg/mL against Pseudomonas aeruginosa resistant to carbapenems. While, the acetylated derivate of (3), compound (3Ac) showed the best cytotoxic result against PC3 (IC50 = 43 ± 4 µg/mL) and Hep3B (IC50 = 49.0 ± 4 µg/mL) cancer cell lines. Likewise, (3Ac) achieved better SI values on HepG2 and Hep3B cell lines. This research reveals the importance of study medicinal plants, to identify bioactive molecules as sources of potential drugs. The presence of these compounds allows us to justify the use of this plant in traditional Mexican medicine.

Synthesis and in vitro evaluation of antimycobacterial and cytotoxic activity of new α,ß-unsaturated amide, oxazoline and oxazole derivatives from l-serine.

The synthesis of 19 compounds derived from l-serine and analogs of p-substituted cinnamic acid is reported. Oxazolines 9 and oxazoles 10 have high antitubercular activity with Minimum Inhibitory Concentration (MIC) of 0.7812-25.0 µg/mL (3.21-100.3 µM), against two strains of Mycobacterium tuberculosis sensitive to first-line drugs Isoniazid (INH), Rifampicin (RIF), Ethambutol (EMB), Pyrazinamide (PZE) (H37Rv) and a clinical isolate resistant to INH, RIF and EMB (G122). The cytotoxic evaluation shows that oxazoles have low activity, finding viability>96% against the VERO cell line. The results show these compounds could be considered as future alternatives for antitubercular treatment.

Hechtia glomerata Zucc: Phytochemistry and Activity of Its Extracts and Major Constituents Against Resistant Bacteria.

Hechtia glomerata Zucc. is used both as a source of food and in ethnomedicine to treat various diseases derived from bacterial infections such as bronchitis, laryngitis, nephritis, whooping cough, urethritis, and sepsis. There are no previous reports about its chemistry and biological activities. Therefore, the aims of this study were to identify components from organic and aqueous extracts of H. glomerata and test the extracts and major isolate compounds against resistant bacteria. Hexane, CHCl3/MeOH, and aqueous extracts were prepared and analyzed by different chromatographic techniques. Structural elucidation was carried out by NMR spectroscopy and X-ray diffraction. The antibacterial activities of extracts, phytochemicals, and semisynthetic derivatives against resistant bacteria were determined by the broth micro-dilution method. From the hexane extract nonacosane (1), hexatriacontanyl stearate (2), hexacosanol (3), oleic acid (4), and ß-sitosterol (5) were isolated and characterized. From the CHCl3/MeOH extract, p-coumaric acid (6), margaric acid (7), caffeic acid (8), daucosterol (9), and potassium chloride (10) were isolated and characterized. A total of 58 volatile compounds were identified by GC-MS from the hexane extract and two solids were isolated from the CHCl3/MeOH extract. The UPLC-QTOF-MS analysis of the aqueous extract allowed the identification of 55 polar compounds. Hexane and aqueous extracts showed antibacterial activity against ESBL Escherichia coli, and three strains of Klebsiella pneumoniae ESBL, NDM-1 +, and OXA-48 with MIC values of 500 µg/mL. The CHCl3/MeOH extract was devoid of activity. The activity of phytocompounds and their semisynthetic derivatives toward resistant bacteria was weak. The most active compound was ß-sitosterol acetate, with a MIC value of 100 µg/mL against carbapenem-resistant A. baumannii. This is the first report of the secondary metabolites of H. glomerata Zucc. and the activity of its extracts and major pure compounds against resistant bacterial strains.

Screening of north-east Mexico medicinal plants with activities against herpes simplex virus and human cancer cell line.

The plants examined in this study have previous biological activity reports indicating the possibility of found activity against herpes and cancer cell. The aim of this contribution was to carry out a screening of Juglans mollis (Juglandaceae), Persea americana (Lauraceae), Hamelia patens (Rubiaceae), Salvia texana (Lamiaceae), Salvia ballotaeflora (Lamiaceae), Ceanothus coeruleus (Rhamnaceae), Chrysactinia mexicana (Asteraceae) y Clematis drummondii (Ranunculaceae), against HeLa cells, VHS-1 and VHS-2. The method MTT was used to determine the 50% cytotoxic concentration (CC50), in Vero and HeLa cell lines. To determine the 50% inhibitory concentration (IC50) against herpes, the plaque reduction method was used. Results showed that none of the plants exhibited activity against HeLa cells. About antiherpetic activity, J. mollis and S. ballotaeflora extracts present antiherpetic activity in terms of their SI, increasingly interest for further studies on the isolation of compounds with antiherpetic activity and about the mechanisms of action that produce this activity.

Chemical composition of Acacia farnesiana (L) wild fruits and its activity against Mycobacterium tuberculosis and dysentery bacteria.

ETHNOPHARMACOLOGICAL RELEVANCE: In Mexico, plants are an important element of traditional medicine, and many are considered part of Mexican cultural heritage from prehispanic and colonial times. Nevertheless, relatively few systematic scientific studies have been conducted to fully characterize the chemical composition and pharmacological activities of Mexican medicinal plants. Acacia farnesiana is used in Mexican traditional medicine to treat dysentery and tuberculosis and therefore could have bioactive compounds that may explain its traditional use. AIMS OF THE STUDY: i) To isolate and characterize the compounds from the hexanic, chloroformic and methanolic extracts; ii) to identify the volatile compounds from methylated hexanic and chloroformic extracts using GC-FID and GC-MS methods; iii) to identify the compounds from methanolic and aqueous extracts using HPLC-Q-TOF-MS; iv) to test the activity of extracts and isolated compounds against Mycobacterium tuberculosis and dysentery bacteria. MATERIAL AND METHODS: A. farnesiana fruits were collected in Acatlán de Osorio, Puebla, Mexico. Hexanic, chloroformic, methanolic and aqueous extracts were prepared and analyzed by different chromatographic techniques including column chromatography, flash chromatography, GC-FID, GC-MS and HPLC-Q-TOF-MS. Structural elucidation was carried out by NMR spectroscopic analysis. The activity of extracts, phytochemicals and semi-synthetic derivatives against Mycobacterium tuberculosis H37Rv and G122 as well as dysentery bacteria (Campylobacter jejuni, Shigella flexneri, Salmonella enteritidis, Yersinia enterocolitica and enterohemorrhagic Escherichia coli) was determined by the broth microdilution method and reported as minimal inhibitory concentration (MIC µg/mL). RESULTS: From both hexane and chloroform extracts, tetracosanoic acid (2S)-2,3-dihydroxypropyl ester (1) and (3ß,22E)-estigmasta-5,22-dien-3-yl ß-D-glucopyranoside (2) were isolated and characterized. From the methanolic extract, methyl gallate (3), gallic acid (4), (3ß,22E)-estigmasta-5,22-dien-3-yl ß-D-glucopyranoside (2), (2S) naringenin 7-O-ß-glucopyranoside (prunin, 5), pinitol (6) and sucrose (7) were isolated and characterized. Furthermore, hexanic and chloroformic extracts were analyzed by GC-FID and GC-MS and 18 methylated fatty acids were identified for each extract in addition to three sterols. The methanolic and aqueous extracts were analyzed separately by HPLC-Q-TOF-MS, and 15 compounds were identified in each extract. The compounds 1, 2, and 7, in addition to 13 fatty acids and eight phenolic compounds, were identified for the first time in A. farnesiana. The extracts showed antitubercular (MIC 100-200 µg/mL) and antidysentery activity (MIC 100-200 µg/mL). Methyl gallate and its acetylated derivative showed activity against the sensible strain M. tuberculosis H37Rv with MIC values of 50-25 µg/mL, respectively. The flavanone prunin showed activity against multidrug resistant M. tuberculosis G122 (MIC 50 µg/mL). Methyl gallate, gallic acid and prunin showed activity against C. jejuni (MIC 50 µg/mL). CONCLUSIONS: The activity of tested extracts and isolated compounds against M. tuberculosis and dysentery bacteria justifies the ethnomedical use of A. farnesiana fruits for the treatment of tuberculosis and dysentery.

Nuclear magnetic resonance spectroscopy data of isolated compounds from Acacia farnesiana (L) Willd fruits and two esterified derivatives.

In the present article we describe the spectroscopic data of 1H and 13C Nuclear Magnetic Resonance of 11 compounds including: Nine natural products from the hexanic-chloroformic and methanolic extracts of Acacia farnesiana fruit and two esterified derivatives (22E-stimasta-5,22-dien- 3ß-acetyl and methyl 3,4,5-triacetyloxybenzoate). Data linked to the research work entitled "Chemical composition of fruits of Acacia farnesiana (L) Willd and its activity against Mycobacterium tuberculosis and dysentery bacteria" (Hernández et al., 2019) [1].

Stereochemistry of a Second Riolozane and Other Diterpenoids from Jatropha dioica.

The dichloromethane extract of the roots of Jatropha dioica afforded riolozatrione (1) and a C-6 epimer of riolozatrione, 6-epi-riolozatrione (2), as a new structure and only the second reported riolozane diterpenoid. The two known diterpenoids jatrophatrione (3) and citlalitrione (4) were also isolated and characterized. Both epimers 1 and 2 are genuine plant constituents, with 2 likely being the biosynthesis precursor of 1 due to the tendency for the quantitative transformation of 2 into 1 under base catalysis. The structural characterization and distinction of the stereoisomers utilized 1H iterative full-spin analysis, yielding complete J-correlation maps that were represented as quantum interaction and linkage tables. The absolute configuration of compounds 1-4 was established by means of vibrational circular dichroism and via X-ray diffraction analysis for 1, 2, and 4. Additionally, the cytotoxic and antiherpetic in vitro activities of the isolates were evaluated.

meso-Dihydroguaiaretic acid derivatives with antibacterial and antimycobacterial activity.

Thirty-three meso-dihydroguaiaretic acid (meso-DGA) derivatives bearing esters, ethers, and amino-ethers were synthesized. All derivatives were tested against twelve drug-resistant clinical isolates of Gram-positive and Gram-negative bacteria, including sensitive (H37Rv) and multidrug-resistant Mycobacterium tuberculosis strains. Among the tested compounds, four esters (7, 11, 13, and 17), one ether (23), and three amino-ethers (30, 31, and 33) exhibited moderate activity against methicillin-resistant Staphylococcus aureus, whereas 30 and 31 showed better results than levofloxacin against vancomycin-resistant Enterococcus faecium. Additionally, nineteen meso-DGA derivatives displayed moderate to potent activity against M. tuberculosis H37Rv with minimum inhibitory concentration (MIC) values ranging from 3.125 to 50µg/mL. Seven meso-DGA derivatives bearing amino-ethers (26-31 and 33) exhibited the lowest MICs against M. tuberculosis H37Rv and G122 strains, with 31 being as potent as ethambutol (MICs of 3.125 and 6.25µg/mL). The presence of positively charged group precursors possessing steric and hydrophobic features (e.g. N-ethylpiperidine moieties in meso-31) resulted essential to significantly increase the antimycobacterial properties of parent meso-DGA as supported by the R-group pharmacophoric and field-based QSAR analyses. To investigate the safety profile of the antimycobacterial compounds, cytotoxicity on Vero cells was determined. The amino-ether 31 exhibited a selectivity index value of 23, which indicate it was more toxic to M. tuberculosis than to mammalian cells. Therefore, 31 can be considered as a promising antitubercular agent for further studies.

Antiherpetic Plants: A Review of Active Extracts, Isolated Compounds, and Bioassays.

Herpes simplex is a disease that is widely distributed throughout the world. It is caused by herpes simplex virus type 1 (HSV-1) and simplex virus type 2 (HSV-2). The drugs of choice for treatment are acyclovir (ACV), Penciclovir (PCV) and other guanine analogues, which have the same mechanism of action. However, due to the constant increase of ACV-resistant strains in immunocompromised patients, it is necessary to find new treatment alternatives. It has been shown that natural products are a good alternative for the treatment of these diseases as well as being an excellent source of compounds with anti-herpetic activity, which may be useful for the development of new drugs and act through a mechanism of action different from ACV and PCV. This paper compiles reports on extracts and compounds isolated from plants that have anti-herpetic activity. We present an analysis of the solvents most widely used for extraction from plants as well as cells and commonly used methods for evaluating cytotoxic and anti-herpetic activity. Families that have a higher number of plants with anti-herpetic activity are evaluated, and we also highlight the importance of studies of mechanisms of action of extracts and compounds with anti-herpetic activity.

Plants from northeast Mexico with anti-HSV activity.

Based on chemotaxonomic and ethno-pharmacological criteria, three Mexican plants (Jatropha dioica, Salvia texana and S. ballotaeflora) were studied for in vitro activity against HSV-1 and HSV-2. Hydro-methanolic extracts were initially evaluated for their toxicity to Vero cells. Both Salvia species displayed cytotoxicity at the lowest dose (125 microg/mL). The J. dioica extract showed only negligible cytotoxicity (CC50 644 microg/mL). Its anti-HSV activity was evaluated using the plaque reduction assay with HSV-1 and HSV-2 (from clinical isolates) infected Vero cells. The hydro-methanolic extract of J. dioica showed IC50s of 280 and 370 microg/mL against HSV-1 and HSV-2, respectively. The n-hexane liquid-liquid partition of J. dioica extract contained the majority of the active principle(s) with IC50 values of 300 and 270 microg/mL for HSV-1 and HSV-2, respectively. Bioassay-guided isolation led to the known diterpene, riolozatrione.

Stereochemical analysis of leubethanol, an anti-TB-active serrulatane, from Leucophyllum frutescens.

Bioactivity-guided fractionation of the methanolic root bark extract of Leucophyllum frutescens led to the identification of leubethanol (1), a new serrulatane-type diterpene with activity against both multi-drug-resistant and drug-sensitive strains of virulent Mycobacterium tuberculosis. Leubethanol (1) was identified by 1D/2D NMR data, as a serrulatane closely related to erogorgiane (2), and exhibited anti-TB activity with minimum inhibitory concentrations in the range 6.25-12.50 µg/mL. Stereochemical evidence for 1 was gleaned from 1D and 2D NOE experiments, from 1H NMR full spin analysis, and by comparison of the experimental vibrational circular dichroism (VCD) spectrum to density functional theory calculated VCD spectra of two diastereomers.