Glucose-6-Phosphatase and α-Glucosidase Inhibitors from Smilax moranensis Roots Identified by Affinity-Directed Fractionation.

The ethanol/water-soluble extracts of the roots of Smilax moranensis M. Martens & Galeotti, Smilacaceae, which have been appreciated since pre-Hispanic times and traditionally used to treat type 2 diabetes in Mexico, were fractionated by the application of the affinity-directed method to identify glucose-6-phosphatase and α-glucosidase inhibitors. Mass spectrometry was used to identify the inhibitor as free ligands after released from the enzymatic complex by denaturing acidic conditions. The affinity study led to the identification of chlorogenic acid as a glucose-6-phosphatase inhibitor, which is the most abundant metabolite present in the analyzed crude drug. In addition, the affinity studies led to the identification of a flavonolignan glycoside as an α-glucosidase inhibitor. In silico analysis with α-glucosidase MAL12 from the yeast Saccharomyces cerevisiae allowed to determine the best conformational rearrangement for the α-glucosidase inhibitors. Graphical abstract. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43450-020-00116-3.

The Peptide AmPep1 Derived from Amaranth Recognizes the Replication Hairpin of TYLCV Disturbing Its Replication Process in Host Plants.

Antiviral compounds targeting viral replicative processes have been studied as an alternative for the control of begomoviruses. Previously, we have reported that the peptide AmPep1 has strong affinity binding to the replication origin sequence of tomato yellow leaf curl virus (TYLCV). In this study, we describe the mechanism of action of this peptide as a novel alternative for control of plant-infecting DNA viruses. When AmPep1 was applied exogenously to tomato and Nicotiana benthamiana plants infected with TYLCV, a decrease in the synthesis of the two viral DNA strands (CS and VS) was observed, with a consequent delay in the development of disease progress in treated plants. The chemical mechanism of action of AmPep1 was deduced using Raman spectroscopy and molecular modeling showing the formation of chemical interactions such as H bonds and electrostatic interactions and the formation of π-π interactions between both biomolecules contributing to tampering with the viral replication.

Structure Elucidation, Conformation, and Configuration of Cytotoxic 6-Heptyl-5,6-dihydro-2 H-pyran-2-ones from Hyptis Species and Their Molecular Docking to α-Tubulin.

Cytotoxic 6-heptyl-5,6-dihydro-2 H-pyran-2-ones are chemical markers of Hyptis (Lamiaceae) and are responsible for some of the therapeutic properties of species with relevance to traditional medicine. The present investigation describes the isolation of known pectinolides A-C (1-3), in addition to the new pectinolides I-M (4-8), from two Mexican collections of H. pectinata by HPLC. The novel biosynthetically related monticolides A (9) and B (10) were also isolated by high-speed countercurrent chromatography from H. monticola, an endemic species of the Brazilian southeastern high-altitude regions. A combination of chemical correlations, chiroptical measurements, and Mosher ester NMR analysis was used to confirm their absolute configuration. The utility of DFT-NMR chemical shifts and JH-H calculations was assessed for epimer differentiation. Molecular docking studies indicated that 6-heptyl-5,6-dihydro-2 H-pyran-2-ones have a high affinity for the pironetin-binding site of α-tubulin, which may be a possible mechanism contributing to the cytotoxic potential of these small and flexible molecules.

HPLC-MS profiling of the multidrug-resistance modifying resin glycoside content of Ipomoea alba seeds

ABSTRACT High performance liquid chromatography profiling with mass spectrometry detection was applicable to identify known and novel multidrug-resistance glycolipid inhibitors from the complex resin glycosides mixture of Ipomoea alba L., Convolvulaceae, seeds. Albinosides X and XI were purified by recycling liquid chromatography and their structural elucidation was accomplished by nuclear magnetic resonance. Albinoside XI exerted a strong potentiation of vinblastine susceptibility in multidrug-resistant human breast carcinoma cells.

Resistance-modifying Activity in Vinblastine-resistant Human Breast Cancer Cells by Oligosaccharides Obtained from Mucilage of Chia Seeds (Salvia hispanica).

The multidrug resistance (MDR) phenotype is considered as a major cause of the failure in cancer chemotherapy. The acquisition of MDR is usually mediated by the overexpression of drug efflux pumps of a P-glycoprotein. The development of compounds that mitigate the MDR phenotype by modulating the activity of these transport proteins is an important yet elusive target. Here, we screened the saponification and enzymatic degradation products from Salvia hispanica seed's mucilage to discover modulating compounds of the acquired resistance to chemotherapeutic in breast cancer cells. Preparative-scale recycling HPLC was used to purify the hydrolysis degradation products. All compounds were tested in eight different cancer cell lines and Vero cells. All compounds were noncytotoxic at the concentration tested against the drug-sensitive and multidrug-resistant cells (IC50  > 29.2 µM). For the all products, a moderate vinblastine-enhancing activity from 4.55-fold to 6.82-fold was observed. That could be significant from a therapeutic perspective. Copyright © 2017 John Wiley & Sons, Ltd.

Resin Glycosides from Ipomoea alba Seeds as Potential Chemosensitizers in Breast Carcinoma Cells.

Multidrug resistance is the expression of one or more efflux pumps, such as P-glycoprotein, and is a major obstacle in cancer therapy. The use of new potent and noncytotoxic efflux pump modulators, coadministered with antineoplastic agents, is an alternative approach for increasing the success rate of therapy regimes with different drug combinations. This report describes the isolation and structure elucidation of six new resin glycosides from moon vine seeds (Ipomoea alba) as potential mammalian multidrug-resistance-modifying agents. Albinosides IV-IX (1-6), along with the known albinosides I-III (7-9), were purified from the CHCl3-soluble extract. Degradative chemical reactions in combination with NMR spectroscopy and mass spectrometry were used for their structural elucidation. Four new glycosidic acids, albinosinic acids D-G (10-13), were released by saponification of natural products 3-6. They were characterized as tetrasaccharides of either convolvulinolic (11S-hydroxytetradecanoic) or jalapinolic (11S-hydroxyhexadecanoic) acids. The potentiation of vinblastine susceptibility in multidrug-resistant human breast carcinoma cells of albinosides 1-6 was evaluated by modulation assays. The noncytotoxic albinosides VII (4) and VIII (5), at a concentration of 25 µg/mL, exerted the strongest potentiation of vinblastine susceptibility, with a reversal factor (RFMCF-7/Vin+) of 201- and >2517-fold, respectively.

Resin glycosides from Ipomoea wolcottiana as modulators of the multidrug resistance phenotype in vitro.

Recycling liquid chromatography was used for the isolation and purification of resin glycosides from the CHCl3-soluble extracts prepared using flowers of Ipomoea wolcottiana Rose var. wolcottiana. Bioassay-guided fractionation, using modulation of both antibiotic activity against multidrug-resistant strains of Gram-negative bacteria and vinblastine susceptibility in breast carcinoma cells, was used to isolate the active glycolipids as modulators of the multidrug resistance phenotype. An ester-type dimer, wolcottine I, one tetra- and three pentasaccharides, wolcottinosides I-IV, in addition to the known intrapilosin VII, were characterized by NMR spectroscopy and mass spectrometry. In vitro assays established that none of these metabolites displayed antibacterial activity (MIC>512 µg/mL) against multidrug-resistant strains of Escherichia coli, and two nosocomial pathogens: Salmonella enterica serovar Typhi and Shigella flexneri; however, when tested (25 µg/mL) in combination with tetracycline, kanamycin or chloramphenicol, they exerted a potentiation effect of the antibiotic susceptibility up to eightfold (64 µg/mL from 512 µg/mL). It was also determined that these non-cytotoxic (CI50>8.68 µM) agents modulated vinblastine susceptibility at 25 µg/mL in MFC-7/Vin(+) cells with a reversal factor (RFMCF-7/Vin(+)) of 2-130 fold.