ABSTRACT
Phytochemical investigation of Sideritis pullulans aerial part and root extracts allowed to isolate six ent-kaurane diterpenes, two phenylpropanoids, and one coumarin, identified as 1α,3α,7ß,18-tetrahydroxy-ent-kaur-16-ene (sideripullol A) (1), 3α,11α,18-trihydroxy-ent-kaur-16-ene (sideripullol B) (2), 3α,7ß,18-trihydroxy-17-nor-ent-kauran-16-one (sideritone A) (3), 3α,7ß-dihydroxy-18-acetyloxy-17-nor-ent-kauran-16-one (sideritone B) (4), 3α,7ß,16α,17-tetrahydroxy-18-acetyloxy-ent-kaurane (sideripullol C) (5), 7ß,16α,17,18-tetrahydroxy-ent-kaurane (sideripullol D) (6), ß-(3-methoxy-4-hydroxyphenyl)-ethyl-O-α-l-arabinopiranosyl-(1â2)-α-l-rhamnopyranosyl-(1â3)-6-O-t-feruloyl-ß-d-glucopyranoside (sideritiside A) (7), ß-(3,4-dihydroxyphenyl)-ethyl-O-α-l-arabinopiranosyl-(1â2)-α-l-rhamnopyranosyl-(1â3)-6-O-t-feruloyl-ß-d-glucopyranoside (sideritiside B) (8), and 7-demethyl-8-methoxycoumarsabin (9), respectively. Twenty known compounds, including phenolics, flavonol glycosides, iridoids, diterpenes, sesquiterpenes, lignans, coumarins, and phenylpropanoids were also isolated and characterized. All diterpenes were evaluated for their cytotoxic activity.
Subject(s)
Diterpenes/chemistry , Phenols/chemistry , Sideritis/chemistry , Cell Line, Tumor , Coumarins/chemistry , Coumarins/isolation & purification , Diterpenes/isolation & purification , HeLa Cells , Humans , Inhibitory Concentration 50 , Molecular Structure , Phenols/isolation & purification , Plant Components, Aerial/chemistry , Plant Roots/chemistryABSTRACT
Four new clerodane diterpenes (1-4) and one new phenylpropanoid (5) have been isolated from Clerodendrum splendens aerial parts, together with nine known compounds. Their structures were determined by spectroscopic and spectrometric analysis and chemical methods. The absolute configuration of the 15,16-diol moiety in 4 was determined by Snatzke's method. Antiproliferative activity of diterpenes in HeLa cells was also evaluated. The IC50 values were 98 ± 11 µM for 3 and 101 ± 8 µM for 1, respectively.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Clerodendrum/chemistry , Diterpenes, Clerodane/isolation & purification , Phenols/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/therapeutic use , Diterpenes, Clerodane/chemistry , Diterpenes, Clerodane/pharmacology , Diterpenes, Clerodane/therapeutic use , HeLa Cells , Humans , Molecular Structure , Neoplasms/drug therapy , Phenols/chemistry , Phenols/pharmacology , Phytotherapy , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Extracts/therapeutic useABSTRACT
Six new benzophenone glycosides, 2,3',4,5',6-pentahydroxybenzophenone 4-O-(6â³-benzoyl)-ß-d-glucopyranoside (1), 2,3',4,5',6-pentahydroxybenzophenone 4-O-ß-d-glucopyranoside (2), 2,3',4,5',6-pentahydroxybenzophenone 2-O-(2â³-benzoyl)-α-l-arabinopyranoside (3), 2,3',4,5',6-pentahydroxybenzophenone 2-O-α-l-arabinopyranoside (4), 2,3',4,5',6-pentahydroxybenzophenone 2-O-(4â³-acetyl)-ß-d-xylopyranoside (5), and 2,3',4,5',6-pentahydroxybenzophenone 3-C-(4â³-benzoyl)-ß-d-glucopyranoside (6), and five known compounds were isolated from the aerial parts of Hypericum humifusum ssp. austral. The structures of 1-6 were elucidated by mass spectrometry and extensive 1D and 2D NMR spectroscopy.
Subject(s)
Benzophenones/isolation & purification , Glycosides/isolation & purification , Hypericum/chemistry , Benzophenones/chemistry , Glycosides/chemistry , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Stereoisomerism , TunisiaABSTRACT
Clerodane diterpenoids are a class of naturally occurring molecules widely distributed in the Lamiaceae family. Neo-clerodane diterpenoids from Salvia ssp were recently described as compounds inhibiting the proliferation of human cancer cell lines. To gain new insights into molecular mechanism(s) underlying the antitumor potential of this class of compounds, we used a chemical proteomics approach to analyse the cellular interactome of hardwickiic acid (HAA) selected as a representative molecule. HAA was linked to an opportune 1,1'-carbonyldiimidazole modified by 1,12-dodecanediamine and then immobilized on a matrix support. The modified beads were then used as bait for fishing the potential partners of HAA in a U937 cell lysate. We identified heat shock protein 27 (Hsp27), an ATP-independent antiapoptotic chaperone characterized for its tumorigenic and metastatic properties and now referenced as a major therapeutic target in many types of cancer, as a major HAA partner. Here, we also report the study of HAA-Hsp27 interaction by means of a panel of chemical and biological approaches, including surface plasmon resonance measurements limited proteolysis, and biochemical assays. Our data suggest that HAA could provide a potential tool to develop strategies for the discovery of Hsp27 chemical inhibitors.
Subject(s)
Antineoplastic Agents, Phytogenic/chemistry , Diterpenes, Clerodane/chemistry , Diterpenes/chemistry , HSP27 Heat-Shock Proteins/chemistry , Plant Extracts/chemistry , Salvia/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Binding Sites , Cell Line, Tumor , Cell Survival/drug effects , Culture Media, Conditioned/chemistry , Diterpenes/isolation & purification , Diterpenes/pharmacology , Diterpenes, Clerodane/isolation & purification , Diterpenes, Clerodane/pharmacology , HSP27 Heat-Shock Proteins/metabolism , Heat-Shock Proteins , Humans , Imidazoles/chemistry , Microspheres , Molecular Chaperones , Protein Binding , Proteolysis , Proteomics/methods , Surface Plasmon ResonanceABSTRACT
Eight compounds, nagilactone C 7-O-α-L-arabinopyranosyl-(1â4)-ß-D-xylopyranoside, nagilactone C 7-O-ß-D-glucopyranosyl-(1â4)-ß-D-xylopyranoside, nagilactone C 7-O-ß-D-xylopyranoside, nagilactone A 7-O-α-L-arabinopyranosyl-(1â4)-ß-D-xylopyranoside, 2ß,15S,16,17,19-pentahydroxy-isopimar-8(14)-ene 17-O-ß-D-glucopyranoside, 2ß,15R,16,17,19-pentahydroxy-isopimar-8(14)-ene 17-O-ß-D-glucopyranoside, 1-(2,6,6-trimethyl-4-hydroxycyclohexenyl)-1-hydroxy-buta-1-en-3-one 4-O-ß-D-glucopyranoside, and vitexin 2â³-O-ß-D-(6'''-acetyl)-glucopyranoside together with 13 known compounds, were isolated from the leaves of Podocarpus elongatus. Structures were elucidated by 1D and 2D NMR spectroscopy as well as by ESI mass spectrometry and chemical methods. The absolute configurations of the 15,16-diol moieties in two compounds were determined using Snatzke's method.