showing 28 related works from this author
Semisynthesis of new tetrahydrofuranic alkyl ester and furano-pyrone derivatives as inhibitors of the mitochondrial complex I
2002
Abstract Methoxymethylation of altholactone ( 1 ) led to the corresponding O -methoxymethyl derivative ( 3 ) in addition to the unexpected 6,7-dihydro-7-methoxy analogue ( 4 ), and two original tetrahydrofuranic (THF) alkyl esters ( 5 , 6 ). Moreover, when we accomplished a new method for the preparation of the furano-pyrone goniofupyrone ( 7 ) through 7-hydroxylation of 1 in acid medium, a minor compound ( 8 ) with an identical skeleton to that of compounds 5 and 6 was identified. Careful examination of the published spectral data of the reported styryl-lactones with an heptolide skeleton reveals that those structures possess also a THF alkyl ester skeleton. The revision of those structure…
ChemInform Abstract: An Efficient Method for the Preparation of Antitumoral α-Keto-imines Benzyldihydroisoquinolines by Selective Benzylic Oxidation …
2010
A series of potent antitumor α-keto-imine BDHIQ derivatives were synthesized and assayed in vitro against L1210 leukemia cell line. A new and easy method for the direct formation of α-keto-imine from imine BDHIQ's was performed with 10% C/Pd in acetonitrile.
3-acetylaltholactone and related styryl-lactones, mitochondrial respiratory chain inhibitors.
2000
A novel furano-pyrone, 3-acetylaltholactone, and two other known styryl-lactones, altholactone and 5-acetoxyisogoniothalamin oxide, have been isolated from Goniothalamus arvensis (Annonaceae) stem bark. We report here the isolation and structural elucidation of these compounds with furane-pyrone and styryl-pyrone skeletons, postulating also for the first time their mechanism of cytotoxicity based on inhibition on mammalian mitochondrial respiratory chain.
Tetrahydroisoquinolines as dopaminergic ligands: 1-Butyl-7-chloro-6-hydroxy-tetrahydroisoquinoline, a new compound with antidepressant-like activity …
2009
International audience; Three series of 1-substituted-7-chloro-6-hydroxy-tetrahydroisoquinolines (1-butyl-, 1-phenyl- and 1-benzyl derivatives) were prepared to explore the influence of each of these groups at the 1-position on the affinity for dopamine receptors. All the compounds displayed affinity for D(1)-like and/or D(2)-like dopamine receptors in striatal membranes, and were unable to inhibit [(3)H]-dopamine uptake in striatal synaptosomes. Different structure requirements have been observed for adequate D(1) or D(2) affinities. This paper details the synthesis, structural elucidation, dopaminergic binding assays, structure-activity relationships (SAR) of these three series of isoquin…
Semisynthesis and cytotoxicity of styryl-lactone derivatives.
1999
The cytotoxicity and the cell-cycle action of altholactone (1), goniofufurone (2), and eight altholactone derivatives (5-12), were determined in vitro on L-1210 cells. Semisyntheses and structure-activity relationships of these compounds are described. The results of this study suggest that the cytotoxicity of altholactone (1), 11-nitro-altholactone (8), and 7-chloro-6,7-dihydroaltholactone (10) is due to the accumulation of the cells in the G2 + M phase of the cell cycle.
Enantiospecific semisynthesis of (+)-almuheptolide-A, a novel natural heptolide inhibitor of the mammalian mitochondrial respiratory chain.
1998
The development of novel styryl lactone derivatives as bioactive compounds and the semisynthesis of both 4,5-dialkoxylated eight-membered-ring lactones with a heptolide skeleton (almuheptolide-A (1) type) and 7-alkoxylated delta-lactones with a saturated furanopyrone skeleton (etharvensin (8) type) have been successfully achieved from the chiral unsaturated alpha-pyrone altholactone (7). This new method is a direct and one-step enantiospecific alkoxylation of altholactone (7) in concentrated acid medium, followed by formation of the eight-membered-ring zeta-lactone. The reaction mechanism operating in the synthesis of the heptolide skeleton is postulated to be a direct Michael-type addition…
Rollimembrin, a novel acetogenin inhibitor of mammalian mitochondrial complex I
1997
Abstract Rollimembrin (3), is a new adjacent bis-tetrahydrofuranic acetogenin with a scarce relative configuration, threo/cis/threo/cis/erythro, isolated from Rollinia membranacea seeds. The mechanism of cytotoxic activity, determined by NADH-oxidase experiments, establish that rollimembrin (3) is the most potent inhibitor of mammalian mitochondrial complex I.
Acetogenins from Annonaceae: Recent Progress in Isolation, Synthesis and Mechanisms of Action
2005
Covering: the literature from 1998 to 2004 The aim of the present review is to summarise the knowledge about newly isolated acetogenins (ACGs) in the last six years. It will also report the total syntheses that have allowed either the confirmation or the revision of some structures, together with the biological activities and mechanism of action of such interesting natural products. In fact, of the 417 isolated compounds reviewed, over 176 have been added during the period from 1998 to 2004.
New antitumoral acetogenin ‘Guanacone type’ derivatives: Isolation and bioactivity. Molecular dynamics simulation of diacetyl-guanacone
2007
We describe herein the isolation and semisynthesis of four acetogenin derivatives (1-4) as well as their ability to inhibit the mitochondrial respiratory chain and several tumor cell lines. In addition, four nanoseconds (ns) of MD simulation of compound 4, in a fully hydrated POPC bilayer, is reported.
Mechanism of vascular relaxation by thaligrisine
2000
Abstract In the present study we examine the mechanism by which thaligrisine, a bisbenzyltetrahydroisoquinoline alkaloid, inhibits the contractile response of vascular smooth muscle. The work includes functional studies on rat isolated aorta and tail artery precontracted with noradrenaline or KCl. In other experiments rat aorta was precontracted by caffeine in the presence or absence of extracellular Ca 2 +. In order to assess whether thaligrisine interacts directly with calcium channel binding sites or with α-adrenoceptors we examined the effect of the alkaloid on [ 3 H]-(+)- cis diltiazem, [ 3 H]-nitrendipine and [ 3 H]-prazosin binding to cerebral cortical membranes. The functional studi…
ChemInform Abstract: Enantioselective Syntheses of Dopaminergic (R)- and (S)-Benzyltetrahydroisoquinolines.
2010
Optically pure (1S,R)- and (1R,S)-benzyltetrahydroisoquinolines (BTHIQs), 12a,b as the major diastereomers, were prepared by stereoselective reduction of the isoquinolinium salt possessing (R)- and (S)-phenylglycinol as the chiral auxiliary, respectively. The absolute configurations of (1S,R)-13a hydrochloride (O-debenzoylated derivative from 12a) and (1R,S)-12b diastereomers were unambiguously determined by single-crystal X-ray analysis. Reductive removal of the chiral auxiliary group, subsequent N-propylation, and cleavage of the methylenedioxy group furnished the optically active catecholamines (1S)-16a and (1R)-16b in good overall yield. We have separately prepared for the first time pa…
Structure-activity relationship of dopaminergic halogenated 1-benzyl-tetrahydroisoquinoline derivatives
2009
Two series of halogenated 1-benzyl-7-chloro-6-hydroxy-tetrahydroisoquinolines were prepared to explore the influence of each series on the affinity for dopamine receptors. All the compounds displayed a high affinity for D(1)-like and/or D(2)-like dopamine receptors in striatal membranes, although they were unable to inhibit [(3)H]-dopamine uptake in striatal synaptosomes. The halogen placed on the benzylic ring in 1-benzyl-THIQs, compounds of the series 1, 2'-bromobenzyl derivatives with K(i) values into the nanomolar range, and the series 2, 2',4'-dichlorobenzyl-THIQ homologues, proves to be an important factor to modulate affinity at dopamine receptor. (C) 2009 Elsevier Masson SAS. All ri…
Gibberellin reactivates and maintains ovary-wall cell division causing fruit set in parthenocarpic Citrus species
2016
[EN] Citrus is a wide genus in which most of the cultivated species and cultivars are natural parthenocarpic mutants or hybrids (i.e. orange, mandarin, tangerine, grapefruit). The autonomous increase in GA(1) ovary concentration during anthesis was suggested as being the stimulus responsible for parthenocarpy in Citrus regardless of the species. To determine the exact GA-role in parthenocarpic fruit set, the following hypothesis was tested: GA triggers and maintains cell division in ovary walls causing fruit set. Obligate and facultative parthenocarpic Citrus species were used as a model system because obligate parthenocarpic Citrus sp (i.e. Citrus unshiu) have higher GA levels and better n…
Efficient synthesis and structural analysis of new dioxopiperazine isoquinolines
2006
Abstract We report herein the synthesis of new dioxopiperazine isoquinolines using the Pictet–Spengler cyclisation. Our synthetic strategy for the preparation of two new compounds ( 5 , 6 ), with a tetrahydro-6H-pyrazino[1,2-b]isoquinoline-1,4-dione moiety was developed in only four steps. To understand better the crucial step of the synthesis reported here, theoretical calculations using semiempirical (PM3), ab initio and DFT computations were carried out on a reduced system model. The structure of chlorohydrate water solvate of tetrahydro (2-piperidinylethyl)-6H-pyrazino [1,2-b]isoquinoline-1,4-dione ( 6·HCl·2H2O ) was determined by X-ray diffraction. Theoretical calculations (RHF/3-21G a…
Inhibitory effects on mitochondrial complex I of semisynthetic mono-Tetrahydrofuran acetogenin derivatives
2003
Modifications in the terminal alpha,beta-unsaturated gamma-methyl-gamma-lactone moiety or in the alkyl chain that links this terminal gamma-lactone with the alpha,alpha'-dihydroxylated THF system of the natural mono-tetrahydrofuranic acetogenins, annonacin and annonacinone, led to the preparation of eight semisynthetic derivatives. Their inhibitory effects on mitochondrial complex I is discussed and compared with that of the classical complex I inhibitor, rotenone.
Preparation of 7-Alkoxylated Furanopyrones: Semisynthesis of (−)-Etharvensin, a New Styryl-Lactone from Goniothalamus arvensis
1997
A new furanopyrone derivative, (−)-etharvensin (1), was isolated from the stem bark of Goniothalamus arvensis. Semisynthesis of the 7-ethoxyfuranopyrone 1 was achieved by addition of EtOH in concentrated acid medium to the unsaturated α-pyrone (+)-altholactone (2). This protocol constitutes a novel, direct (single-step), and efficient method to prepare this class of bioactive compounds.
Styryl-pyrones from Goniothalamus arvensis
1998
Two novel styrl-pyrones, (+)-garvensintriol and (+)-etharvendiol, together with a known cytotoxic furano-furone, (+)-goniofufurone, have been isolated from the stem bark of Goniothalamus arvensis. A different relative configuration, cis-erythro-erythro for garvensintriol and cis-threo-erythro for etharvendiol, is established, and their absolute stereochemistry is discussed.
Tucumanin, a β-hydroxy-γ-lactone bistetrahydrofuranic acetogenin from Annona cherimolia, is a potent inhibitor of mitochondrial complex I
2004
A new β-hydroxy-γ-methyl-γ-lactone bistetrahydrofuranic acetogenin, tucumanin, with the infrequent symmetrical threo/trans/threo/trans/ threo relative configuration at the tetrahydrofuran rings was isolated from Annona cherimolia (Annonaceae) seeds. The inhibitory potency on the mitochondrial complex I of acetogenins with this relative configuration (tucumanin and asimicin) was compared with that shown by the corresponding pairs with an asymmetrical threo/trans/threo/trans/erythro relative configuration (laherradurin/rolliniastatin-2, and itrabin/molvizarin). All these compounds act as selective inhibitors of mitochondrial complex 1 in the 0.18 - 1.55 nM range. Fil: Barrachina, Isabel. Univ…
Syntheses of dopaminergic 1-cyclohexylmethyl-7,8-dioxygenated tetrahydroisoquinolines by selective heterogeneous tandem hydrogenation
2002
Abstract We describe the preparation in a ‘one-pot’ sequence 1-cyclohexylmethyl 7,8-dioxygenated tetrahydroisoquinoline, substituted and unsubstituted in the C ring by application of the Photo–Fries transposition, followed by a tandem reduction–cyclization and further reduction. Indeed, we have accomplished for the first time regioselective hydrogenation of the benzylic ring of the tetrahydroisoquinoline systems. All 1-cyclohexylmethyl THIQ synthesized were able to displace D2 dopamine receptor from its specific binding site in rat striatal membranes, while the N-methylated derivatives showed also affinity for D1 dopamine receptors.
Styryl-lactones from the stem bark of Goniothalamus arvensis
1999
The fractionation of the methanolic extract of Goniothalamus arvensis (Annonaceae) stem bark led to the isolation of two novel styryl-lactones, arvensin and (+)-2-epi-altholactone. The structures of these compounds, which belong to the furano-pyrone group, were established on the basis of mass spectrometry, one- and two-dimensional nuclear magnetic resonance experiments, as well as simple chemical derivatization. The relative and absolute configurations of the compounds are discussed. Copyright © 1999 John Wiley & Sons, Ltd.
Polycerasoidol, a Natural Prenylated Benzopyran with a Dual PPARα/PPARγ Agonist Activity and Anti-inflammatory Effect
2019
Dual peroxisome proliferator-activated receptor-α/γ (PPARα/γ) agonists regulate both lipid and glucose homeostasis under different metabolic conditions and can exert anti-inflammatory activity. We investigated the potential dual PPARα/γ agonism of prenylated benzopyrans polycerasoidol (1) and polycerasoidin (2) and their derivatives for novel drug development. Nine semisynthetic derivatives were prepared from the natural polycerasoidol (1) and polycerasoidin (2), which were evaluated for PPARα, -γ, -δ and retinoid X receptor-α activity in transactivation assays. Polycerasoidol (1) exhibited potent dual PPARα/γ agonism and low cytotoxicity. Structure–activity relationship studies revealed th…
Tetrandrine and Isotetrandrine, Two Bisbenzyltetrahydroisoquinoline Alkaloids from Menispermaceae, with Rat Uterine Smooth Muscle Relaxant Activity
1992
Abstract The effects of two bisbenzyltetrahydroisoquinoline alkaloids, 1S, 1′S tetrandrine and its isomer 1R, 1′S isotetrandrine, were investigated in rat isolated uterus in order to identify the mechanism of relaxant action and to study the influence of the absolute configuration on the activity of these alkaloids. Both inhibited the uterine contraction induced by high K+, acetylcholine and oxytocin. In Ca2+-free medium, isotetrandrine relaxed the sustained contraction induced by oxytocin but tetrandrine did not. The relaxant effects of the alkaloids may be due to blockade of calcium influx through specific channels. Tetrandrine and isotetrandrine modify the calcium channel in a nonreversi…
Synthesis of N-diisopropyl phosphoryl benzyl-tetrahydroisoquinoline, a new class of mitochondrial complexes I and III inhibitors
2000
The synthesis of N-(O,O-diisopropylphosphoryl)-benzyltetrahydroisoquinoline (3) has been achieved in a 'one pot' procedure from imine (2) and diisopropyl-phosphorochloridate (1) generated in situ (POCl3 + iPrOH). Compound 3 is the first benzyltetrahydroisoquinoline derivative found to be a potent inhibitor of mitochondrial complexes I and III, and therefore it opens a new perspective with this series of compounds as they can be considered as new class of antitumor agents.
Synthesis of benzopyran derivatives as PPARα and/ or PPARγ activators
2019
International audience; We describe the synthesis of 26 compounds, small polycerasoidol analogs, that are Lipinski’s rule-of-five compliant. In order to confirm key structural features to activate PPARα and/or PPARγ, we have adopted structural modifications in the following parts: (i) the benzopyran core (hydrophobic nucleus) by benzopyran-4-one, dihydrobenzopyran or benzopyran-4-ol; (ii) the side chain at 2-position by shortening to C3, C4 and C5-carbons versus C-9-carbons of polycerasoidol; (iii) the carboxylic group (polar head) by oxygenated groups (hydroxyl, acetoxy, epoxide, ester, aldehyde) or non-oxygenated motifs (allyl and alkyl). Benzopyran-4-ones 6, 12, 13 and 17 as well as dihy…
Conformational study of N-alkyl-benzyltetrahydroisoquinolines alkaloid
2003
Abstract An exhaustive conformational study on the benzyltetrahydroisoquinolines (BTHIQ) from ab initio (RHF/6-31G(d)) calculations was carried out. The effects of different substituents at chiral C 1 atom were also considered. Our results indicate that different substituents at C 1 in BTHIQ molecules introduce a significant steric hindrance which, in turn, might be responsible for a conformational restriction favouring or disfavouring the spatial orientation of the lone pairs of N atom allowing or not the electronic attachment with the side chain of Asp residue. These results can serve as an aid for designing suitable structures of BTHIQs for better dopamine D 1 -receptor inhibitory activi…
Enantioselective syntheses of dopaminergic (R)- and (S)-benzyltetrahydroisoquinolines.
2001
Optically pure (1S,R)- and (1R,S)-benzyltetrahydroisoquinolines (BTHIQs), 12a,b as the major diastereomers, were prepared by stereoselective reduction of the isoquinolinium salt possessing (R)- and (S)-phenylglycinol as the chiral auxiliary, respectively. The absolute configurations of (1S,R)-13a hydrochloride (O-debenzoylated derivative from 12a) and (1R,S)-12b diastereomers were unambiguously determined by single-crystal X-ray analysis. Reductive removal of the chiral auxiliary group, subsequent N-propylation, and cleavage of the methylenedioxy group furnished the optically active catecholamines (1S)-16a and (1R)-16b in good overall yield. We have separately prepared for the first time pa…
Styryl-lactones from Goniothalamus species— A review
1999
Thirty-one bioactive styryl-lactones, with six different basic skeletons, have been isolated from Goniothalamus species. Aspects of their isolation, structural elucidation, biogenesis and biological activity are reviewed. Copyright © 1999 John Wiley & Sons, Ltd.
An efficient method for the preparation of antitumoral α-keto-imines benzyldihydroisoquinolines by selective benzylic oxidation with C/Pd in acetonit…
2002
A series of potent antitumor α-keto-imine BDHIQ derivatives were synthesized and assayed in vitro against L1210 leukemia cell line. A new and easy method for the direct formation of α-keto-imine from imine BDHIQ's was performed with 10% C/Pd in acetonitrile.