Verónica M. Rivas-Galindo

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.

Antibacterial and Antimycobacterial Lignans and Flavonoids from Larrea tridentata

Three lignans and four flavonoids were isolated and characterized from Larrea tridentata and compounds were tested against 16 bacterial species/strains. Results showed that: dihydroguaiaretic acid (1) had activity towards methicillin resistant (MR) Staphylococcus aureus (minimum inhibitory concentration (MIC) 50 µg/mL) and multidrug‐resistant (MDR) strains of Mycobacterium tuberculosis (MIC 12.5–50 µg/mL); 4‐epi‐larreatricin (2) was active against Enterobacter cloacae (MIC 12.5 µg/mL), as well as sensitive (MIC 50 µg/mL) and MDR strains of M. tuberculosis (MIC 25 µg/mL). 3′‐Demethoxy‐6‐O‐demethylisoguaiacin (3) displayed activity against sensitive and resistant S. aureus (MIC 25 µg/mL), Enterococcus faecalis (MIC 12.5 µg/mL), Escherichia coli (MIC 50 µg/mL), E. cloacae (MIC 12.5 µg/mL) and MDR strains of M. tuberculosis (MIC 12.5 µg/mL). 5,4′‐Dihydroxy‐3,7,8,3′‐tetramethoxyflavone (4) and 5,4′‐dihydroxy‐3,7,8‐trimethoxyflavone (5) were active against M. tuberculosis MDR strains having MIC values of 25 and 25–50 µg/mL, respectively, while 5,4′‐dihydroxy‐7‐methoxyflavone (6) was active against S. aureus (MIC 50 µg/mL) and E. faecalis (MIC 50 µg/mL). We concluded that lignan 3 is the main compound responsible for the antibacterial activity of L. tridentata. Lignans 1 and 2 as well as flavonoid 6 contribute with some degree of antibacterial activity. On the other hand, compounds 1, 2, 3, 4 and 5 contributed to the antimycobacterial activity found in L. tridentata. Copyright

Activity against Streptococcus pneumoniae of the Essential Oil and δ-Cadinene Isolated from Schinus molle Fruit

Abstract Streptococcus pneumoniae is a major cause of respiratory infections. This study aims to test the activity of the essential oil obtained from the fruit of Schinus molle against S. pneumoniae resistant to conventional antibiotics and to identify the compounds responsible for the activity. A fraction showing antimicrobial activity (MIC 125 μg/mL) was obtained. The principal components were identified as: β-myrcene (39.7%), p-cymene (19.5%), δ-cadinene (7.8%), α-phellandrene (7.1%) and limonene (4.1%). Bioassay-guided fractionation led to the identification of δ-cadinene as the principal active constituent (MIC of 31.25 μg/mL). The findings reported here highlight and justify the global spread of the use of S. molle for the treatment of respiratory infections.

Biologically active anthracenones from roots of Karwinskia parvifolia

Tullidinol, a neurotoxin isolated from fruits and roots of several Karwinskia species, was resolved for the first time into two stereoisomers. This was achieved by means of preparative HPLC from roots of Karwinskia parvifolia. Structural assignments were made on the basis of spectroscopic data, including long range correlations as well as geometry optimization by means of semi-empirical methods.

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.

Determination of Isoperoxisomicine A1 Content in Peroxisomicine A1 Batches by Means of 1H NMR

Abstract Peroxisomicine A1 (PA1) is a natural product that shows biological activity. After its extraction and isolation from the plant, there is still between 3 and 5% remaining of an isomer (isoperoxisomicine A1, isoPA1), which is also present in the original matrix. A simple and reliable quantification method has been developed by means of proton nuclear magnetic resonance spectroscopy to determine the isoperoxisomicine amount in these PA1 batches. Two methods were applied to the quantification: the relative area method and an absolute method by using an internal standard. No significant differences were found between them. The simplicity of the first one makes it desirable for routine analysis. The validated method has adequate linearity and precision, because it allows measuring as low as 1% of isoPA1 content.

Antimicrobial Activity of Plants Used in México for Gastrointestinal and Respiratory Disorders

Here, we review the literature on Mexican plants and their products as antifungal and antibacterial agents; the results strongly support the contention that traditional medicine remains a valuable resource in the potential discovery of natural product pharmaceuticals. We found that 297 species belonging to 224 genera and 102 families had been tested; from the plants screened, 103 extracts were active against Gram positive bacteria, 47 extracts against M. tuberculosis, 106 extracts were active against Gram negative bacteria, and 64 extracts were active against fungi. The methanolic extracts resulted in the most active extracts against Gram-positive and Gram-negative bacteria. M. tuberculosis was more sensitive to nonpolar extracts. Additionally, 54 compounds resulted active against bacteria and 22 against fungi. Therefore, this review is a good resource for future development of research into the antimicrobial activity of medicinal plants growing in Mexico.

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

Abstract 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) Willd 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 (3β,22E)-estigmasta-5,22-dien-3-yl β-D-glucopyranoside (2) were isolated and characterized. From the methanolic extract, methyl gallate (3), gallic acid (4), (3β,22E)-estigmasta-5,22-dien-3-yl β-D-glucopyranoside (2), (2S) naringenin 7-O-β-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.

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.