Diego Cortés | Universidad Nacional de Colombia (original) (raw)

Papers by Diego Cortés

Research paper thumbnail of Antispasmodic Activity of Benzylisoquinoline Alkaloids Analogous to Papaverine

Planta Medica, 1993

In vitro, reticuline, norarmepavine, coclaurine, and papaverine competitively antagonize the uter... more In vitro, reticuline, norarmepavine, coclaurine, and papaverine competitively antagonize the uterine muscular contractions induced by acetylcholine and calcium. The antagonism is more efficient for the alkaloid coclaurine which is even stronger than papaverine. The pA2 values obtained with each of the four alkaloids for both agents, acetylcholine and calcium, respectively, were as follows: reticuline (5.35 and 4.81), norarmepavine (5.55 and 4.09), coclaurine (7.42 and 6.91), papaverine (5.32 and 6.23). The two components, phasic and tonic, of the response of the vas deferens to potassium are reduced by the four alkaloids. The reduction is greater for the tonic phase, with the following IC50 values: reticuline 474 microM, norarmepavine 101 microM, coclaurine 68.9 microM, and papaverine 14.3 microM. The antispasmodic activity of the three alkaloids, similar to papaverine, is related to an inhibiting effect of extracellular calcium, an intracellular effect, or both.

Research paper thumbnail of The Plant NADPH Oxidase RBOHD Mediates Rapid Systemic Signaling in Response to Diverse Stimuli

Science Signaling, 2009

The following resources related to this article are available online at http://stke.sciencemag.org.

Research paper thumbnail of Methylation of Gibberellins by Arabidopsis GAMT1 and GAMT2

Plant Cell, 2007

Arabidopsis thaliana GAMT1 and GAMT2 encode enzymes that catalyze formation of the methyl esters ... more Arabidopsis thaliana GAMT1 and GAMT2 encode enzymes that catalyze formation of the methyl esters of gibberellins (GAs). Ectopic expression of GAMT1 or GAMT2 in Arabidopsis, tobacco (Nicotiana tabacum), and petunia (Petunia hybrida) resulted in plants with GA deficiency and typical GA deficiency phenotypes, such as dwarfism and reduced fertility. GAMT1 and GAMT2 are both expressed mainly in whole siliques (including seeds), with peak transcript levels from the middle until the end of silique development. Within whole siliques, GAMT2 was previously shown to be expressed mostly in developing seeds, and we show here that GAMT1 expression is also localized mostly to seed, suggesting a role in seed development. Siliques of null single GAMT1 and GAMT2 mutants accumulated high levels of various GAs, with particularly high levels of GA 1 in the double mutant. Methylated GAs were not detected in wild-type siliques, suggesting that methylation of GAs by GAMT1 and GAMT2 serves to deactivate GAs and initiate their degradation as the seeds mature. Seeds of homozygous GAMT1 and GAMT2 null mutants showed reduced inhibition of germination, compared with the wild type, when placed on plates containing the GA biosynthesis inhibitor ancymidol, with the double mutant showing the least inhibition. These results suggest that the mature mutant seeds contained higher levels of active GAs than wild-type seeds.

Research paper thumbnail of Natural acetogenins from annonaceae, synthesis and mechanisms of action

Phytochemistry, 1998

The search concerning Annonaceous acetogenins has increased in the last two years. The goal of th... more The search concerning Annonaceous acetogenins has increased in the last two years. The goal of the present review is to summarize the knowledge about new isolated acetogenins as well as the advances in synthesis, biological activity and mechanism of action.

Research paper thumbnail of Specific interactions of monotetrahydrofuranic annonaceous acetogenins as inhibitors of mitochondrial complex I

Chemico-biological Interactions, 1999

Annonaceous acetogenins (ACG) are a wide group of cytotoxic compounds isolated from plants of the... more Annonaceous acetogenins (ACG) are a wide group of cytotoxic compounds isolated from plants of the Annonaceae family. Some of them are promising candidates to be a future new generation of antitumor drugs due to the ability to inhibit the NADH:ubiquinone oxidoreductase of the respiratory chain (mitochondrial complex I), main gate of the energy production in the cell. ACG are currently being tested on standard antitumor trials although little is known about the structure-activity relationship at the molecular level. On recent studies, the relevance of several parts of the molecule for the inhibitory potency has been evaluated. Due to the great diversity of skeletons included in this family of natural products, previous studies on the presence and distribution of oxygenated groups along the alkyl chain only covered the compounds with different bis-tetrahydrofuranic (bis-THF) relative configurations. Therefore, we have investigated the inhibitory action of all the mono-tetrahydrofuranic (mono-THF) acetogenins available, which differ in the oxygenated arrangements along the molecule. Our results show that the hydroxyl and carbonyl groups, placed in the aliphatic chain that links the initial g-lactone moiety with the dihydroxylated tetrahydrofuranic ring system, significantly contribute for modulating the inhibitory potency of the ACG through specific effects. : S 0 0 0 9 -2 7 9 7 ( 9 9 ) 0 0 1 2 0 -9 J. Tormo et al. /

Research paper thumbnail of Murisolin: A New Cytotoxic Mono-tetrahydrofuran-g-lactone from Annona muricata

Research paper thumbnail of Acetogenins from annonaceae, inhibitors of mitochondrial complex I

Phytochemistry, 1996

Pergamon 00319422(95)008365 Phytochemist, Vol. 42. No. 2, pp. 253271, 1996 Copyright ) 1996 Elsev... more Pergamon 00319422(95)008365 Phytochemist, Vol. 42. No. 2, pp. 253271, 1996 Copyright ) 1996 Elsevier Science Lid Printed in Great Britain. All rights reserved 00319422 96 15.00 + 0.00 REVIEW ARTICLE NUMBER 112 ACETOGENINS FROM ANNONACEAE, INHIBITORS ...

Research paper thumbnail of Norstephalagine et Atherospermidine, Deux Aporphines d'Artabotrys maingayi Relaxantes du Muscle Lisse

Journal of Natural Products, 1990

Assmm.-Nine isoquinoline alkaloids have been isolated from the bark of Artabotrys maingayi: four ... more Assmm.-Nine isoquinoline alkaloids have been isolated from the bark of Artabotrys maingayi: four noraporphines (norstephalagine 111, 3-hydroxynornuciferine, anonaine, and nornuciferine), one 7-hydroxyaporphine (ushinsunine), three oxoaporphines ( ...

Research paper thumbnail of Corossolone et corossoline, deux nouvelles γ-lactones mono-tétrahydrofuraniques cytotoxiques

Canadian Journal of Chemistry-revue Canadienne De Chimie, 1991

The fractionation by solvents of the contents of the seeds of Annona muricata (Annonaceae), guide... more The fractionation by solvents of the contents of the seeds of Annona muricata (Annonaceae), guided by the toxic activity towards the brine shrimp larva and the KB cancer cells, has enabled us to isolate two new cytotoxic mono-tetrahydrofuran γ-lactones: corossolone 1 ...

Research paper thumbnail of Styryl-lactones from Goniothalamus species— A review

Phytochemical Analysis, 1999

Thirty-one bioactive styryl-lactones, with six different basic skeletons, have been isolated from... more 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.

Research paper thumbnail of Effects of Various Isoquinoline Alkaloids on In Vitro 3 H-Dopamine Uptake by Rat Striatal Synaptosomes

Journal of Natural Products, 1995

Various alkaloids having an isoquinoline skeleton from different species of the Annonaceae, Fumar... more Various alkaloids having an isoquinoline skeleton from different species of the Annonaceae, Fumariacae, and Aristolochiacae (aporphine, cularine, benzylisoquinoline, and bisbenzylisoquinoline derivatives) were tested for their ability to inhibit in vitro 3H-dopamine uptake by rat striatal dopamine D1 3H-SCH 23390 AND D2 3H-raclopride binding sites. Except for some aporphine derivatives (anonaine [1], norstephalagine [2], isopiline [3]) and some bisbenzylisoquinoline alkaloids (dimethylgrisabine [27], antioquine [28], obaberine [29], isotetrandrine [30]) that displayed affinities of the same order as the reference compounds (nomifensine [38], amineptine [39], dexamphetamine [40]), the other tested products had low, or no, affinity on the 3H-dopamine uptake since, in comparison, its affinity at dopamine D1 3H-SCH 23390 and D2 3H-raclopride binding sites was low. These data suggest that it could be possible to synthesize anonaine-like products displaying intense dopamine-uptake inhibitory properties, which could lead to a potential antidepressant activity.

Research paper thumbnail of 3-Acetylaltholactone and related styryl-lactones, mitochondrial respiratory chain inhibitors

Phytochemistry, 2000

A novel furano-pyrone, 3-acetylaltholactone, and two other known styryl-lactones, altholactone an... more 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.

Research paper thumbnail of Antiparasitic Activity of Annona muricata and Annona cherimolia Seeds

Planta Medica, 1991

Methanolic extracts of Annona muricata and A. cherimolia (Annonaceae) seeds were tested for antip... more Methanolic extracts of Annona muricata and A. cherimolia (Annonaceae) seeds were tested for antiparasitic activity against E. histolytica, N. brasiliensis, M. dessetae and A. salina. The acetogenins isolated from these extracts are found to be responsible for the important activity on infective larvae of Molinema desetae.

Research paper thumbnail of Syntheses and Antitumor Targeting G1 Phase of the Cell Cycle of Benzoyldihydroisoquinolines and Related 1-Substituted Isoquinolines

Journal of Medicinal Chemistry, 2002

A series of 1-substituted 3,4-dihydroisoquinolines were synthesized and tested in vitro against t... more A series of 1-substituted 3,4-dihydroisoquinolines were synthesized and tested in vitro against the leukemia L 1210 cell line to evaluate their ability to perturb the cell cycle by arresting cells in the G1 phase. 1-Benzoylimines, 1-phenylimines, and 1-alkylimines were synthesized. The most powerful cytotoxic derivatives, 1-benzoyl-3,4-dihydroisoquinolines (1-26), were obtained from amides I via 1-benzyl-3,4-dihydroisoquinoline in good yield by a direct selective oxidation of the benzylic carbon of the corresponding imines through 10% Pd/C in acetonitrile. SAR studies let us to identify the essential structural features for cytotoxic activity. The most bioactive compounds (with IC(50) < 5 microM) were BzDHIQ (13, 22, 21, 8, 9, 11, 1, 20, 6, and 19), and they are characterized by the following: (i) An alpha-ketoimine moiety is necessary for potent antiproliferative activity (1-phenyl- and 1-alkyl-3,4-dihydroisoquinoline derivatives, 34-40, are less active). (ii) An hydrophobic, benzyloxy, alkyloxy, or allyloxy group at the C-6 position seems to be relevant for cytotoxicity. (iii) Regarding the influence of the benzoylic moiety, both the unsubstituted (13, 8, 9, 11, 1, and 6) and the 3'-monosubstituted (22, 21, 20, and 19) compounds were more potent than compounds with other substitutions.

Research paper thumbnail of Insecticidal and Mutagenic Evaluation of Two Annonaceous Acetogenins

Journal of Natural Products, 2000

Annonaceous acetogenins represent a new class of bioactive compounds whose primary mode of action... more Annonaceous acetogenins represent a new class of bioactive compounds whose primary mode of action is the inhibition of NADH-ubiquinone oxidoreductase. Given the potential pesticidal use of such a class of compounds, we have further evaluated the antifeedant and insecticidal effects of squamocin and annonacin, two annonaceous acetogenins, on Spodoptera littoralis, Leptinotarsa decemlineata, and Myzus persicae. Additionally, to partially assess their environmental risk, we have also tested their mutagenicity in Salmonella typhimurium strains TA98, TA100, and TA102 in the presence and absence of a metabolic activation system. Among the test compounds, annonacin showed antifeedant effects on L. decemlineata, while squamocin was toxic to L. decemlineata and M. persicae. Neither acetogenin was mutagenic, although both were toxic in the absence of a metabolic activation system. We compared these results with those obtained with rotenone, a well-known respiratory inhibitor that was highly toxic to L. decemlineata and M. persicae and showed no mutagenicity/toxicity in the S. typhimurium strains tested up to a concentration of 1000 microg per plate.

Research paper thumbnail of Styryl-pyrones from Goniothalamus arvensis

Phytochemistry, 1998

Two novel styrl-pyrones, (+)-garvensintriol and (+)-etharvendiol, together with a known cytotoxic... more Two novel styrl-pyrones, (+)-garvensintriol and (+)-etharvendiol, together with a known cytotoxic furano-furone, (+)-goniofufurone, have been isolated from the stem bark of Goniothulamus urzwwis. A different relative configuration, cis-rryrhro-erythro for garvensintriol and cis-three-erythro for etharvendiol, is established, and their absolute stereochemistry is discussed. &~3

Research paper thumbnail of Synthesis and Dopamine Receptor Selectivity of the Benzyltetrahydroisoquinoline, ( R )-( + )- nor -Roefractine

Journal of Natural Products, 1998

R)-(+)-nor-Roefractine (1) was synthesized by the Bischler-Napieralski route, using asymmetric re... more R)-(+)-nor-Roefractine (1) was synthesized by the Bischler-Napieralski route, using asymmetric reduction of the 1,2-didehydro precursor imine with sodium (S)-N-CBZ-prolinyloxyborohydride. Compound 1 was able to displace [ 3 H]-raclopride (a D 2 dopamine receptor-selective ligand) from its specific binding sites in rat striatum with selectivity vs [ 3 H]-SCH23390 (D 1 dopamine receptor-selective ligand).

Research paper thumbnail of Rioclarine et Membranacine, Deux Nouvelles Acetogenines Bis-tetrahydrofuraniques des Graines de Rollinia membranacea

Journal of Natural Products, 1993

Arsrucr.-The fractionation of the cytotoxic MeOH extract of the seeds of Rollinia 4 umcu (Annonac... more Arsrucr.-The fractionation of the cytotoxic MeOH extract of the seeds of Rollinia 4 umcu (Annonaceae) led to the isolation of two new adjacent bis-tetrahydrofuran acetoge-nins, rioclarin [l] and membranacin 121, and two other known acetogenins, squamocin [3] and ...

Research paper thumbnail of Goniotharvensin, A Novel Styryl-Lactone from the Stem Bark of Goniothalamus arvensis

Natural Product Letters, 1995

Abstract The fractionation of the MeOH extract from the stem bark of Goniothalamus arvensis (Anno... more Abstract The fractionation of the MeOH extract from the stem bark of Goniothalamus arvensis (Annonaceae) led to the isolation of a new styryl-lactone,(+)-goniotharvensin (1), and two other known styryl-lactones:(+)-altholactone (2) and (+)-isoaltholactone (3). ...

Research paper thumbnail of Kinetic Characterization of Mitochondrial Complex I Inhibitors Using Annonaceous Acetogenins

Archives of Biochemistry and Biophysics, 1999

The NADH:ubiquinone oxidoreductase (complex I) of the mitochondrial respiratory chain is by far t... more The NADH:ubiquinone oxidoreductase (complex I) of the mitochondrial respiratory chain is by far the largest and most complicated of the proton-translocating enzymes involved in the oxidative phosphorylation. Many clues regarding the electron pathways from matrix NADH to membrane ubiquinone and the links of this process with the translocation of protons are highly controversial. Different types of inhibitors become valuable tools to dissect the electron and proton pathways of this complex enzyme. Therefore, further knowledge of the mode of action of complex I inhibitors is needed to understand the underlying mechanism of energy conservation. This study presents for the first time a detailed exploration of the inhibitory action of the Annonaceous acetogenins, the most powerful inhibitors of the mammalian enzyme, taking as the head-series rolliniastatin-1, rolliniastatin-2, and corossolin. Despite their close chemical resemblance, each of them inhibits the complex I with different kinetic features reflecting differential binding to the enzyme.

Research paper thumbnail of Antispasmodic Activity of Benzylisoquinoline Alkaloids Analogous to Papaverine

Planta Medica, 1993

In vitro, reticuline, norarmepavine, coclaurine, and papaverine competitively antagonize the uter... more In vitro, reticuline, norarmepavine, coclaurine, and papaverine competitively antagonize the uterine muscular contractions induced by acetylcholine and calcium. The antagonism is more efficient for the alkaloid coclaurine which is even stronger than papaverine. The pA2 values obtained with each of the four alkaloids for both agents, acetylcholine and calcium, respectively, were as follows: reticuline (5.35 and 4.81), norarmepavine (5.55 and 4.09), coclaurine (7.42 and 6.91), papaverine (5.32 and 6.23). The two components, phasic and tonic, of the response of the vas deferens to potassium are reduced by the four alkaloids. The reduction is greater for the tonic phase, with the following IC50 values: reticuline 474 microM, norarmepavine 101 microM, coclaurine 68.9 microM, and papaverine 14.3 microM. The antispasmodic activity of the three alkaloids, similar to papaverine, is related to an inhibiting effect of extracellular calcium, an intracellular effect, or both.

Research paper thumbnail of The Plant NADPH Oxidase RBOHD Mediates Rapid Systemic Signaling in Response to Diverse Stimuli

Science Signaling, 2009

The following resources related to this article are available online at http://stke.sciencemag.org.

Research paper thumbnail of Methylation of Gibberellins by Arabidopsis GAMT1 and GAMT2

Plant Cell, 2007

Arabidopsis thaliana GAMT1 and GAMT2 encode enzymes that catalyze formation of the methyl esters ... more Arabidopsis thaliana GAMT1 and GAMT2 encode enzymes that catalyze formation of the methyl esters of gibberellins (GAs). Ectopic expression of GAMT1 or GAMT2 in Arabidopsis, tobacco (Nicotiana tabacum), and petunia (Petunia hybrida) resulted in plants with GA deficiency and typical GA deficiency phenotypes, such as dwarfism and reduced fertility. GAMT1 and GAMT2 are both expressed mainly in whole siliques (including seeds), with peak transcript levels from the middle until the end of silique development. Within whole siliques, GAMT2 was previously shown to be expressed mostly in developing seeds, and we show here that GAMT1 expression is also localized mostly to seed, suggesting a role in seed development. Siliques of null single GAMT1 and GAMT2 mutants accumulated high levels of various GAs, with particularly high levels of GA 1 in the double mutant. Methylated GAs were not detected in wild-type siliques, suggesting that methylation of GAs by GAMT1 and GAMT2 serves to deactivate GAs and initiate their degradation as the seeds mature. Seeds of homozygous GAMT1 and GAMT2 null mutants showed reduced inhibition of germination, compared with the wild type, when placed on plates containing the GA biosynthesis inhibitor ancymidol, with the double mutant showing the least inhibition. These results suggest that the mature mutant seeds contained higher levels of active GAs than wild-type seeds.

Research paper thumbnail of Natural acetogenins from annonaceae, synthesis and mechanisms of action

Phytochemistry, 1998

The search concerning Annonaceous acetogenins has increased in the last two years. The goal of th... more The search concerning Annonaceous acetogenins has increased in the last two years. The goal of the present review is to summarize the knowledge about new isolated acetogenins as well as the advances in synthesis, biological activity and mechanism of action.

Research paper thumbnail of Specific interactions of monotetrahydrofuranic annonaceous acetogenins as inhibitors of mitochondrial complex I

Chemico-biological Interactions, 1999

Annonaceous acetogenins (ACG) are a wide group of cytotoxic compounds isolated from plants of the... more Annonaceous acetogenins (ACG) are a wide group of cytotoxic compounds isolated from plants of the Annonaceae family. Some of them are promising candidates to be a future new generation of antitumor drugs due to the ability to inhibit the NADH:ubiquinone oxidoreductase of the respiratory chain (mitochondrial complex I), main gate of the energy production in the cell. ACG are currently being tested on standard antitumor trials although little is known about the structure-activity relationship at the molecular level. On recent studies, the relevance of several parts of the molecule for the inhibitory potency has been evaluated. Due to the great diversity of skeletons included in this family of natural products, previous studies on the presence and distribution of oxygenated groups along the alkyl chain only covered the compounds with different bis-tetrahydrofuranic (bis-THF) relative configurations. Therefore, we have investigated the inhibitory action of all the mono-tetrahydrofuranic (mono-THF) acetogenins available, which differ in the oxygenated arrangements along the molecule. Our results show that the hydroxyl and carbonyl groups, placed in the aliphatic chain that links the initial g-lactone moiety with the dihydroxylated tetrahydrofuranic ring system, significantly contribute for modulating the inhibitory potency of the ACG through specific effects. : S 0 0 0 9 -2 7 9 7 ( 9 9 ) 0 0 1 2 0 -9 J. Tormo et al. /

Research paper thumbnail of Murisolin: A New Cytotoxic Mono-tetrahydrofuran-g-lactone from Annona muricata

Research paper thumbnail of Acetogenins from annonaceae, inhibitors of mitochondrial complex I

Phytochemistry, 1996

Pergamon 00319422(95)008365 Phytochemist, Vol. 42. No. 2, pp. 253271, 1996 Copyright ) 1996 Elsev... more Pergamon 00319422(95)008365 Phytochemist, Vol. 42. No. 2, pp. 253271, 1996 Copyright ) 1996 Elsevier Science Lid Printed in Great Britain. All rights reserved 00319422 96 15.00 + 0.00 REVIEW ARTICLE NUMBER 112 ACETOGENINS FROM ANNONACEAE, INHIBITORS ...

Research paper thumbnail of Norstephalagine et Atherospermidine, Deux Aporphines d'Artabotrys maingayi Relaxantes du Muscle Lisse

Journal of Natural Products, 1990

Assmm.-Nine isoquinoline alkaloids have been isolated from the bark of Artabotrys maingayi: four ... more Assmm.-Nine isoquinoline alkaloids have been isolated from the bark of Artabotrys maingayi: four noraporphines (norstephalagine 111, 3-hydroxynornuciferine, anonaine, and nornuciferine), one 7-hydroxyaporphine (ushinsunine), three oxoaporphines ( ...

Research paper thumbnail of Corossolone et corossoline, deux nouvelles γ-lactones mono-tétrahydrofuraniques cytotoxiques

Canadian Journal of Chemistry-revue Canadienne De Chimie, 1991

The fractionation by solvents of the contents of the seeds of Annona muricata (Annonaceae), guide... more The fractionation by solvents of the contents of the seeds of Annona muricata (Annonaceae), guided by the toxic activity towards the brine shrimp larva and the KB cancer cells, has enabled us to isolate two new cytotoxic mono-tetrahydrofuran γ-lactones: corossolone 1 ...

Research paper thumbnail of Styryl-lactones from Goniothalamus species— A review

Phytochemical Analysis, 1999

Thirty-one bioactive styryl-lactones, with six different basic skeletons, have been isolated from... more 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.

Research paper thumbnail of Effects of Various Isoquinoline Alkaloids on In Vitro 3 H-Dopamine Uptake by Rat Striatal Synaptosomes

Journal of Natural Products, 1995

Various alkaloids having an isoquinoline skeleton from different species of the Annonaceae, Fumar... more Various alkaloids having an isoquinoline skeleton from different species of the Annonaceae, Fumariacae, and Aristolochiacae (aporphine, cularine, benzylisoquinoline, and bisbenzylisoquinoline derivatives) were tested for their ability to inhibit in vitro 3H-dopamine uptake by rat striatal dopamine D1 3H-SCH 23390 AND D2 3H-raclopride binding sites. Except for some aporphine derivatives (anonaine [1], norstephalagine [2], isopiline [3]) and some bisbenzylisoquinoline alkaloids (dimethylgrisabine [27], antioquine [28], obaberine [29], isotetrandrine [30]) that displayed affinities of the same order as the reference compounds (nomifensine [38], amineptine [39], dexamphetamine [40]), the other tested products had low, or no, affinity on the 3H-dopamine uptake since, in comparison, its affinity at dopamine D1 3H-SCH 23390 and D2 3H-raclopride binding sites was low. These data suggest that it could be possible to synthesize anonaine-like products displaying intense dopamine-uptake inhibitory properties, which could lead to a potential antidepressant activity.

Research paper thumbnail of 3-Acetylaltholactone and related styryl-lactones, mitochondrial respiratory chain inhibitors

Phytochemistry, 2000

A novel furano-pyrone, 3-acetylaltholactone, and two other known styryl-lactones, altholactone an... more 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.

Research paper thumbnail of Antiparasitic Activity of Annona muricata and Annona cherimolia Seeds

Planta Medica, 1991

Methanolic extracts of Annona muricata and A. cherimolia (Annonaceae) seeds were tested for antip... more Methanolic extracts of Annona muricata and A. cherimolia (Annonaceae) seeds were tested for antiparasitic activity against E. histolytica, N. brasiliensis, M. dessetae and A. salina. The acetogenins isolated from these extracts are found to be responsible for the important activity on infective larvae of Molinema desetae.

Research paper thumbnail of Syntheses and Antitumor Targeting G1 Phase of the Cell Cycle of Benzoyldihydroisoquinolines and Related 1-Substituted Isoquinolines

Journal of Medicinal Chemistry, 2002

A series of 1-substituted 3,4-dihydroisoquinolines were synthesized and tested in vitro against t... more A series of 1-substituted 3,4-dihydroisoquinolines were synthesized and tested in vitro against the leukemia L 1210 cell line to evaluate their ability to perturb the cell cycle by arresting cells in the G1 phase. 1-Benzoylimines, 1-phenylimines, and 1-alkylimines were synthesized. The most powerful cytotoxic derivatives, 1-benzoyl-3,4-dihydroisoquinolines (1-26), were obtained from amides I via 1-benzyl-3,4-dihydroisoquinoline in good yield by a direct selective oxidation of the benzylic carbon of the corresponding imines through 10% Pd/C in acetonitrile. SAR studies let us to identify the essential structural features for cytotoxic activity. The most bioactive compounds (with IC(50) < 5 microM) were BzDHIQ (13, 22, 21, 8, 9, 11, 1, 20, 6, and 19), and they are characterized by the following: (i) An alpha-ketoimine moiety is necessary for potent antiproliferative activity (1-phenyl- and 1-alkyl-3,4-dihydroisoquinoline derivatives, 34-40, are less active). (ii) An hydrophobic, benzyloxy, alkyloxy, or allyloxy group at the C-6 position seems to be relevant for cytotoxicity. (iii) Regarding the influence of the benzoylic moiety, both the unsubstituted (13, 8, 9, 11, 1, and 6) and the 3'-monosubstituted (22, 21, 20, and 19) compounds were more potent than compounds with other substitutions.

Research paper thumbnail of Insecticidal and Mutagenic Evaluation of Two Annonaceous Acetogenins

Journal of Natural Products, 2000

Annonaceous acetogenins represent a new class of bioactive compounds whose primary mode of action... more Annonaceous acetogenins represent a new class of bioactive compounds whose primary mode of action is the inhibition of NADH-ubiquinone oxidoreductase. Given the potential pesticidal use of such a class of compounds, we have further evaluated the antifeedant and insecticidal effects of squamocin and annonacin, two annonaceous acetogenins, on Spodoptera littoralis, Leptinotarsa decemlineata, and Myzus persicae. Additionally, to partially assess their environmental risk, we have also tested their mutagenicity in Salmonella typhimurium strains TA98, TA100, and TA102 in the presence and absence of a metabolic activation system. Among the test compounds, annonacin showed antifeedant effects on L. decemlineata, while squamocin was toxic to L. decemlineata and M. persicae. Neither acetogenin was mutagenic, although both were toxic in the absence of a metabolic activation system. We compared these results with those obtained with rotenone, a well-known respiratory inhibitor that was highly toxic to L. decemlineata and M. persicae and showed no mutagenicity/toxicity in the S. typhimurium strains tested up to a concentration of 1000 microg per plate.

Research paper thumbnail of Styryl-pyrones from Goniothalamus arvensis

Phytochemistry, 1998

Two novel styrl-pyrones, (+)-garvensintriol and (+)-etharvendiol, together with a known cytotoxic... more Two novel styrl-pyrones, (+)-garvensintriol and (+)-etharvendiol, together with a known cytotoxic furano-furone, (+)-goniofufurone, have been isolated from the stem bark of Goniothulamus urzwwis. A different relative configuration, cis-rryrhro-erythro for garvensintriol and cis-three-erythro for etharvendiol, is established, and their absolute stereochemistry is discussed. &~3

Research paper thumbnail of Synthesis and Dopamine Receptor Selectivity of the Benzyltetrahydroisoquinoline, ( R )-( + )- nor -Roefractine

Journal of Natural Products, 1998

R)-(+)-nor-Roefractine (1) was synthesized by the Bischler-Napieralski route, using asymmetric re... more R)-(+)-nor-Roefractine (1) was synthesized by the Bischler-Napieralski route, using asymmetric reduction of the 1,2-didehydro precursor imine with sodium (S)-N-CBZ-prolinyloxyborohydride. Compound 1 was able to displace [ 3 H]-raclopride (a D 2 dopamine receptor-selective ligand) from its specific binding sites in rat striatum with selectivity vs [ 3 H]-SCH23390 (D 1 dopamine receptor-selective ligand).

Research paper thumbnail of Rioclarine et Membranacine, Deux Nouvelles Acetogenines Bis-tetrahydrofuraniques des Graines de Rollinia membranacea

Journal of Natural Products, 1993

Arsrucr.-The fractionation of the cytotoxic MeOH extract of the seeds of Rollinia 4 umcu (Annonac... more Arsrucr.-The fractionation of the cytotoxic MeOH extract of the seeds of Rollinia 4 umcu (Annonaceae) led to the isolation of two new adjacent bis-tetrahydrofuran acetoge-nins, rioclarin [l] and membranacin 121, and two other known acetogenins, squamocin [3] and ...

Research paper thumbnail of Goniotharvensin, A Novel Styryl-Lactone from the Stem Bark of Goniothalamus arvensis

Natural Product Letters, 1995

Abstract The fractionation of the MeOH extract from the stem bark of Goniothalamus arvensis (Anno... more Abstract The fractionation of the MeOH extract from the stem bark of Goniothalamus arvensis (Annonaceae) led to the isolation of a new styryl-lactone,(+)-goniotharvensin (1), and two other known styryl-lactones:(+)-altholactone (2) and (+)-isoaltholactone (3). ...

Research paper thumbnail of Kinetic Characterization of Mitochondrial Complex I Inhibitors Using Annonaceous Acetogenins

Archives of Biochemistry and Biophysics, 1999

The NADH:ubiquinone oxidoreductase (complex I) of the mitochondrial respiratory chain is by far t... more The NADH:ubiquinone oxidoreductase (complex I) of the mitochondrial respiratory chain is by far the largest and most complicated of the proton-translocating enzymes involved in the oxidative phosphorylation. Many clues regarding the electron pathways from matrix NADH to membrane ubiquinone and the links of this process with the translocation of protons are highly controversial. Different types of inhibitors become valuable tools to dissect the electron and proton pathways of this complex enzyme. Therefore, further knowledge of the mode of action of complex I inhibitors is needed to understand the underlying mechanism of energy conservation. This study presents for the first time a detailed exploration of the inhibitory action of the Annonaceous acetogenins, the most powerful inhibitors of the mammalian enzyme, taking as the head-series rolliniastatin-1, rolliniastatin-2, and corossolin. Despite their close chemical resemblance, each of them inhibits the complex I with different kinetic features reflecting differential binding to the enzyme.