[Show abstract][Hide abstract] ABSTRACT: The first macrocyclic bisdesmoside resin glycoside, jalapinoside (4), was purified by preparative-scale recycling HPLC from the MeOH-soluble extracts of Ipomoea purga roots, the officinal jalap. Purgic acid C (3), a new glycosidic acid of ipurolic acid, was identified as 3-O-β-d-quinovopyranoside, 11-O-β-d-quinovopyranosyl-(1→2)-O-β-d-glucopyranosyl-(1→3)-O-[β-d-fucopyranosyl-(1→4)]-O-α-l-rhamnopyranosyl-(1→2)-O-β-d-glucopyranosyl-(1→2)-O-β-d-quinovopyranoside (3S,11S)-dihydroxytetradecanoic acid. The acylating residues of this core were acetic, (+)-(2S)-methylbutanoic, and dodecanoic acids. The site of lactonization was defined as C-3 of the second saccharide moiety. Reversal of multidrug resistance by this noncytotoxic compound was evaluated in vinblastine-resistant human breast carcinoma cells.
[Show abstract][Hide abstract] ABSTRACT: A comprehensive conformational analysis for the anticancer agent pironetin (1) was achieved by molecular modeling using density functional theory calculations at the B3PW91/DGTZVP level in combination with calculated and experimental (1)H-(1)H coupling constants comparison. Two solvent-dependent conformational families (L and M) were revealed for the optimum conformations. Docking studies of the pironetin-tubulin complex determined a quantitative model for the hydrogen-bond interactions of pironetin through the αAsn249, αAsn258, and αLys352 amino groups in α-tubulin, which supported the formation of a covalent adduct between the αLys352 and the β carbon atom of the α,β-unsaturated lactone. Saturation-transfer difference NMR spectroscopy confirmed that pironetin binds to tubulin, while molecular dynamics exposed a distortion of the tubulin secondary structure at the H8 and H10 α-helices as well as at the S9 β-sheet, where αLys352 is located. A large structural perturbation in the M-loop geometry between the αIle274 and αLeu285 residues, an essential region for molecular recognition between α-α and β-β units of protofilaments, was also identified and provided a rationale for the pironetin inhibitory activity.
The Journal of Organic Chemistry 04/2014; 79(9). DOI:10.1021/jo500420j · 4.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Native to tropical America, Ipomoea batatas has been cultivated for over 5000 years in Mexico. The yellow-skinned tuber crop variety, with an orange flesh, has a higher nutritional value than potato. Raw sweet potato can cause a purge due to its resin glycoside content. Purification of the chloroform-soluble resin glycosides from the roots of this variety was accomplished by preparative-scale HPLC, which allowed for the collection of six oligosaccharides, batatin VII (1) and batatinosides VII-IX (2-4), all of novel structure, together with the known resin glycosides pescaprein I and batatinoside IV. High-field NMR spectroscopy and FAB mass spectrometry were used to characterize each structure, identifying operculinic acid A for compounds 2 and 4, and simonic acid B for 3, as their pentasaccharide glycosidic cores. Batatin VII (1) represents a dimer of the know batatinoside IV, consisting of two units of simonic acid B.
Journal of Agricultural and Food Chemistry 09/2013; 61(39). DOI:10.1021/jf402952d · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Reinvestigation of the CHCl3-soluble extract from the flowers of Ipomoea murucoides, through preparative-scale recycling HPLC, yielded three pentasaccharides of 11-hydroxyhexadecanoic acid, murucoidins XVII-XIX, in addition to the known murucoidin III and V, all of which were characterized by NMR spectroscopy and mass spectrometry. These compounds were found to be macrolactones of the known pentasaccharides simonic acid B and operculinic acid A. The acylating groups corresponded to acetic, (2S)-methyl-butyric, (E)-cinnamic and octanoic acids. The esterification sites were established at the C-2 of the second rhamnose and C-3 and C-4 of the third rhamnose. The aglycone lactonization was placed at C-2 or C-3 of the first rhamnose. Bioassays for modulation of antibiotic activity were performed against multidrug-resistant strains of Staphylococcus aureus, Escherichia coli Rosetta-gami, and two nosocomial pathogens: Salmonella enterica sv. Typhi and Shigella flexneri. The tested glycolipids did not act as cytotoxic (IC50>4μg/mL) nor as antimicrobial (MIC>128μg/mL) agents. However, they exerted a potentiation effect on clinically useful antibiotics against the tested bacteria by increasing their antibiotic susceptibility up to four-fold at concentrations of 25μg/mL.
[Show abstract][Hide abstract] ABSTRACT: Tricolorin A acts as pre- and post-emergence plant growth inhibitor. In pre-emergence it displays broad-spectrum weed control, inhibiting germination of both monocotyledonous (Lolium mutliflorum and Triticum vulgare) and dicotyledonous (Physalis ixocarpa and Trifolium alexandrinum) seeds, being the dicotyledonous seeds the most inhibited. Tricolorin A also inhibited seedling growth, and seed respiration, and since the concentrations required for inhibiting both germination and respiration were similar, we suggest that respiration is one of its targets. Tricolorin A at 60 µM acts as a post- emergence plant growth inhibitor by reducing dry plant biomass by 62%, 37%, 33%, and 22% for L. multiflorum, T. alexandrinum, T. vulgare, and P. ixocarpa, respectively, 18 days after its application. In order to determine the potency of tricolorin A as a plant growth inhibitor, paraquat was used as control; the results indicate that tricolorin A acts as a non-selective post-emergence plant growth inhibitor similar to paraquat, since both reduced the biomass production in P. ixocarpa and T. alexandrinum. Therefore, we suggest that tricolorin A will be a good biodegradable herbicide for weeds.
[Show abstract][Hide abstract] ABSTRACT: The (6'S)-configuration of brevipolides A-J (1-10), isolated from Hyptis brevipes, was established by X-ray diffraction analysis of 9 in conjunction with Mosher's ester analysis of the tetrahydro derivative 11 obtained from both geometric isomers 8 and 9 as well as by chemical correlations. The structure of the new brevipolide J (10) was characterized through NMR and MS data as having the same 6-heptyl-5,6-dihydro-2H-pyran-2-one framework possessing the cyclopropane moiety of all brevipolides but substituted by an isoferuloyl group instead of the p-methoxycinnamoyl moiety found in 8 and 9. Conformational analysis of these cytotoxic 6-heptyl-5,6-dihydro-α-pyrones was carried out on compound 9 by application of a protocol based on comparison between experimental and DFT-calculated vicinal (1)H-(1)H NMR coupling constants. Molecular modeling was used to correlate minimum energy conformers and observed electronic circular dichroism transitions for the isomeric series of brevipolides. Compounds 7-10 exhibited moderate activity (ED(50) 0.3-8.0 μg/mL) against a variety of tumor cell lines.
[Show abstract][Hide abstract] ABSTRACT: Reinvestigation of the CHCl(3)-soluble extract from aerial parts of Ipomoea purga was carried out to identify mammalian multidrug-resistance inhibitors. Preparative-scale recycling HPLC was used to purify four new resin glycosides, purgins II (1) and III (2) in addition to purginosides III (3) and IV (4), as well as the known purginosides I (5) and II (6) and purgin I (7). The structures of 1-4 were established through NMR spectroscopy and mass spectrometry. Purgins II (1) and III (2) are the first examples of ester-type dimers of operculinic acid B with three different acylating residues in both monomeric units: (2S)-methylbutyric acid, n-hexanoic, n-decanoic, and trans-cinnamic acids. The macrolactonization site was located at C-2 of the second saccharide unit. The position of the ester linkage for monomeric unit B on the macrocyclic unit A was established as C-4 of the terminal glucose. Purginosides III (3) and IV (4) were found to be pentasaccharides of operculinic acid A with a structure related to that previously described for compounds 5 and 6. Reversal of multidrug resistance by compounds 1-7 was evaluated in vinblastine-resistant human breast carcinoma cells (MCF-7/Vin). Purgin II (1) enhanced vinblastine activity >2140-fold when incorporated at 25 μg/mL. For compounds 2-7, a moderate vinblastine-enhancing activity from 1.4-fold to 6.5-fold was observed.
[Show abstract][Hide abstract] ABSTRACT: As part of an ongoing project to identify inhibitors of multidrug efflux pumps, three new resin glycosides, albinosides I-III (1-3), were isolated from a CHCl(3)-soluble extract from the seeds of moon vine (Ipomoea alba). Their structures were established through NMR spectroscopy and mass spectrometry as partially acylated branched pentasaccharides derived from three new glycosidic acids, named albinosinic acids A-C (4-6). The same oligosaccharide core formed by two d-quinovose, one d-glucose, and two l-rhamnose units was linked to either convolvulinolic or jalapinolic acid for 1 and 3, respectively. They were partially esterified with (2R,3R)-3-hydroxy-2-methylbutanoic, acetic, or 2-methyl-2-butenoic acid. Compound 2 has two d-quinovose and three l-rhamnose units, linked to convolvulinolic acid, and its esterifying residues were characterized as two units of 2-methyl-2-butenoic acid. The aglycone lactonization site was located at C-2 of the terminal rhamnose unit (Rha) for 1, at C-3 of the terminal rhamnose unit (Rha') for 2, and at C-3 of the second saccharide unit (Glc) for 3. Reversal of multidrug resistance by this class of plant metabolites was also evaluated in vinblastine-resistant human breast carcinoma cells (MCF-7/Vin). The noncytotoxic compound 3 exerted the strongest potentiation effect of vinblastine susceptibility to over 2140-fold, while a moderate activity was observed for 1 (3.1-fold) and 2 (2.6-fold) at a concentration of 25 μg/mL.
[Show abstract][Hide abstract] ABSTRACT: Commercial preparations of the Mexican herbal drug known as "miracle tea" (Packera candidissima and P. bellidifolia) have been profiled qualitatively by HPLC and GC-MS. Eremophilanes (3-7) were the major components found in the hexane-soluble fraction, while pyrrolizidine alkaloids (PAs) were identified in the alkaloid extracts. The content of free PAs and their N-oxides was determined for a total of 22 samples, and the results showed that the amount of these hepatotoxic compounds (0.0005-0.94% free PAs; 0.0004-0.55% N-oxides), through the presence of retrorsine (1) and senesionine (2) as the main constituents, may reach toxic levels. Hexane-soluble extracts from commercial presentations (dried whole plants) of both species afforded neoadenostylone (3), 6-(2-methylbutanoyloxy)-9-oxo-1-(10)-furanoeremophilene (4), and epineoadenostylone (5), in addition to methyl-4-hydroxyphenylacetate (8) and methyl-2-(1-hydroxy-4-oxocyclohexyl)acetate (9). Also, epicacalone (6) and the new compound 2β-hydroxyneoadenostylone (7) were isolated from P. bellidifolia.
[Show abstract][Hide abstract] ABSTRACT: Twenty-six microbiologically inactive (MIC > 512 µg/mL) convolvulaceous resin glycosides ( 1- 26) were tested for resistance modulatory activity in vitro against Escherichia coli Rosetta-gami and two nosocomial pathogens, Salmonella typhi and Shigella flexneri. These compounds exerted a potentiation effect of the clinically useful antibiotics tetracycline, kanamycin, and chloramphenicol against the tested gram-negative bacteria by increasing antibiotic susceptibility up to 32-fold at concentrations of 25 µg/mL. Therefore, the oligosaccharides from the morning glory family (Convolvulaceae) represent metabolites that reverse microbial resistance mechanisms, favoring an increase in the strength and effectiveness of current antibiotics that are not effective in the treatment of refractive infections caused by multidrug-resistant strains.
[Show abstract][Hide abstract] ABSTRACT: Reversal of multidrug resistance (MDR) by thirty resin glycosides from the morning glory family (Convolvulaceae) was evaluated in vinblastine-resistant human breast carcinoma cells (MCF-7/Vin). The effects of these amphipathic compounds on the cytotoxicity and P-glycoprotein (P-gp)-mediated MDR were estimated with the sulforhodamine B colorimetric assay. Active noncytotoxic compounds exerted a potentiation effect of vinblastine susceptibility by 1- to over 1906-fold at tested concentrations of 5 and 25 μg/mL. Murucoidin V (1) enhanced vinblastine activity 255-fold when incorporated at 25 μg/mL and also, based on flow cytometry, significantly increased the intracellular accumulation of rhodamine 123 with the use of reserpine as a positive control for a MDR reversal agent. Incubation of MCF-7/Vin cells with 1 caused an increase in uptake and notably lowered the efflux rate of rhodamine 123. Decreased expression of P-glycoprotein by compound 1 was detected by immunofluorescence flow cytometry after incubation with an anti-P-gp monoclonal antibody. These results suggest that resin glycosides represent potential efflux pump inhibitors for overcoming MDR in cancer therapy.