RESUMEN
Nucleophilic additions of lithium keto and ester enolates and mono- and bifunctional Grignard reagents to artemisitene provided C-16-derived artemisinin monomers, dimers, trimers, and tetramers whose antimalarial and cytotoxic activities have been evaluated.
Asunto(s)
Antimaláricos/síntesis química , Antineoplásicos/síntesis química , Artemisininas , Sesquiterpenos/química , Sesquiterpenos/síntesis química , Animales , Antimaláricos/química , Antimaláricos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular , Chlorocebus aethiops , Cristalografía por Rayos X , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Conformación Molecular , Plasmodium falciparum/efectos de los fármacos , Polímeros , Sesquiterpenos/farmacología , Relación Estructura-Actividad , Células Tumorales CultivadasAsunto(s)
Antibióticos Antineoplásicos/aislamiento & purificación , Antimaláricos/aislamiento & purificación , Escarabajos/microbiología , Furanos/aislamiento & purificación , Hypocreales/metabolismo , Tropolona/aislamiento & purificación , Animales , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/metabolismo , Antibióticos Antineoplásicos/farmacología , Antimaláricos/química , Antimaláricos/metabolismo , Antimaláricos/farmacología , Chlorocebus aethiops , Furanos/química , Furanos/metabolismo , Furanos/farmacología , Humanos , Hypocreales/crecimiento & desarrollo , Espectroscopía de Resonancia Magnética , Plasmodium falciparum/efectos de los fármacos , Tropolona/análogos & derivados , Tropolona/química , Tropolona/metabolismo , Tropolona/farmacología , Células Tumorales Cultivadas , Células VeroRESUMEN
Phomoxanthones A (1) and B (2), two novel xanthone dimers, were isolated from the endophytic fungus Phomopsis sp. BCC 1323. Structures of 1 and 2 were elucidated by spectroscopic methods. These compounds exhibited significant in vitro antimalarial and antitubercular activities and cytotoxicity.
Asunto(s)
Antimaláricos/aislamiento & purificación , Antineoplásicos/aislamiento & purificación , Antituberculosos/aislamiento & purificación , Ascomicetos/química , Xantenos/aislamiento & purificación , Xantonas , Animales , Antimaláricos/química , Antimaláricos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Antituberculosos/química , Antituberculosos/farmacología , Carcinoma de Células Escamosas , Chlorocebus aethiops , Femenino , Humanos , Concentración 50 Inhibidora , Leucemia , Espectroscopía de Resonancia Magnética , Ratones , Estructura Molecular , Mycobacterium tuberculosis/efectos de los fármacos , Plasmodium falciparum/efectos de los fármacos , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de Fourier , Estereoisomerismo , Relación Estructura-Actividad , Tailandia , Células Tumorales Cultivadas/efectos de los fármacos , Células Vero/efectos de los fármacos , Xantenos/química , Xantenos/farmacologíaRESUMEN
Bioassay-guided fractionation of the extracts from the insect pathogenic fungus Cordyceps nipponica BCC 1389 led to the isolation of N-hydroxy- and N-methoxy-2-pyridones, cordypyridones A-D (1-4). Structures of these compounds, including absolute configuration, were determined by spectroscopic methods, chemical conversions and single-crystal X-ray diffraction analyses. Codypyridones A and B, atropisomers of each other, exhibited potent in vitro antimalarial activity with IC(50) values of 0.066 and 0.037 microg/mL, respectively, while their cytotoxicity was much weaker.
Asunto(s)
Antimaláricos/química , Hongos/química , Animales , Antimaláricos/aislamiento & purificación , Supervivencia Celular/efectos de los fármacos , Cristalografía por Rayos X , Femenino , Humanos , Concentración 50 Inhibidora , Estructura Molecular , Plasmodium falciparum/efectos de los fármacos , Piridonas/química , Piridonas/aislamiento & purificación , Análisis Espectral , Estereoisomerismo , Células Tumorales CultivadasRESUMEN
Three known compounds, 2-hexylidene-3-methylsuccinic acid (1), cytochalasin Q (2), and 5-carboxymellein (3), together with two new derivatives, 2-hexylidene-3-methylsuccinic acid 4-methyl ester (4) and an ophiobolane sesterterpene named halorosellinic acid (5), were isolated from culture broth of the marine fungus Halorosellinia oceanica BCC 5149. Compounds 1-3 exhibited moderate cytotoxicity against KB and BC-1 cell lines with IC(50) values of 1-13 microg/mL, while compounds 2, 3, 5, and 6 showed antimalarial activity with respective IC(50) values of 17, 4, 13, and 19 microg/mL. Halorosellinic acid (5) possessed only weak antimycobacterial activity with the minimum inhibitory concentration of 200 microg/mL.
Asunto(s)
Antimaláricos/farmacología , Mycobacteriaceae/efectos de los fármacos , Plasmodium falciparum/efectos de los fármacos , Terpenos/farmacología , Animales , Antimaláricos/síntesis química , Citocalasinas/síntesis química , Citocalasinas/farmacología , Hongos/química , Humanos , Concentración 50 Inhibidora , Isocumarinas , Células KB , Pruebas de Sensibilidad Microbiana , Ocratoxinas/síntesis química , Ocratoxinas/farmacología , Sesterterpenos , Succinatos/síntesis química , Succinatos/farmacología , Terpenos/síntesis químicaRESUMEN
Two new 10-membered lactones, namely, multiplolides A (1) and B (2), were isolated from the broth extract of the fungus Xylaria multiplex BCC 1111. Chemical structures of 1 and 2 were elucidated on the basis of their spectral data. Multiplolides A (1) and B (2) exhibited antifungal activity against Candida albicans with IC(50) values of 7 and 2 microg/mL, respectively. Both 1 and 2 were inactive in the screening systems toward the malarial parasite Plasmodium falciparum (at 20 microg/mL) and were not cytotoxic to BC-1 and KB cell lines (at 20 microg/mL).
Asunto(s)
Antifúngicos/aislamiento & purificación , Lactonas/aislamiento & purificación , Animales , Antifúngicos/química , Antifúngicos/farmacología , Ascomicetos/química , Candida albicans/efectos de los fármacos , Candida albicans/metabolismo , Células Cultivadas/efectos de los fármacos , Humanos , Células KB/efectos de los fármacos , Lactonas/química , Lactonas/farmacología , Espectroscopía de Resonancia Magnética , Estructura Molecular , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/metabolismo , Estereoisomerismo , Relación Estructura-Actividad , TailandiaRESUMEN
Stereospecific deprotonation of the epoxy proton at the beta-position of the alpha,beta-epoxy esters 5 and 6 yielded oxiranyl "remote" anions 7 and 8, which could then be used for alkylation. The anions 7 and 8 underwent a consecutive aldol lactonization to give, respectively, epoxy lactones 11 and 13 with high stereoselectivity. Generation of the remote anions as well as their stereoselective reactions served as a new synthetic route to the naturally occurring alpha-methylenebis-gamma-butyrolactones, 1.
Asunto(s)
Furanos/síntesis química , Furanos/química , Conformación Molecular , Penicillium/química , Sporothrix/químicaRESUMEN
Bioassay-guided fractionation of the cell extract of the insect pathogenic fungus Aschersonia tubulata BCC 1785 led to the isolation of dustanin (1), 3 beta,15 alpha,22-trihydroxyhopane (3), 5 alpha,8 alpha-epidioxy-24(R)-methylcholesta-6,22-diene-3 beta-ol (6), together with the new 3 beta-acetoxy-15 alpha,22-dihydroxyhopane (4). Chemical structures of these compounds were elucidated by spectral analyses as well as chemical transformation. Compounds 1 and 4 exhibited antimycobacterial activity with the minimum inhibitory concentration (MIC) of 12.5 micrograms/ml.
Asunto(s)
Antibacterianos/aislamiento & purificación , Hypocreales/química , Triterpenos/aislamiento & purificación , Animales , Antibacterianos/química , Antibacterianos/farmacología , Bioensayo , Humanos , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Conformación Molecular , Mycobacterium tuberculosis/efectos de los fármacos , Triterpenos/química , Triterpenos/farmacologíaRESUMEN
New furanoid labdane diterpenes, potamogetonyde (3) and potamogetonol (4), together with two known compounds, potamogetonin (1) and 15,16-epoxy-12-oxo-8(17),13(16),14-labdatrien-20,19-olide (2), were isolated from the CH(2)Cl(2) extract of Potamogeton malaianus. The chemical structures of 1-4 were elucidated by the analyses of their spectral data, mainly by 1D and 2D NMR techniques. Potamogetonyde (3) and potamogetonol (4) exhibited potent antiviral (HSV-1) activity with respective IC(50) values of 8 and 3 microg/mL. Compounds 1-4 possessed cytotoxicity toward insect cells (fall armyworm and mosquito larvae, IC(50) of 11-72 microg/mL). Furanoid diterpenes 3 and 4 also exhibited cytotoxicity against the Vero cell line with respective IC(50)'s of 31 and 28 microg/mL, while 1 and 2 were inactive at 50 microg/mL. Compounds 1-4 were inactive (at 20 microg/mL) against KB and BC cell lines and showed only weak antimycobacterial activity against Mycobacterium tuberculosis H37Ra with minimum inhibitory concentrations of 50-100 microg/mL.
Asunto(s)
Antivirales/aislamiento & purificación , Diterpenos/aislamiento & purificación , Furanos/aislamiento & purificación , Aedes , Animales , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Antituberculosos/química , Antituberculosos/aislamiento & purificación , Antituberculosos/farmacología , Antivirales/química , Antivirales/farmacología , Línea Celular , Chlorocebus aethiops , Citotoxinas/química , Citotoxinas/aislamiento & purificación , Citotoxinas/farmacología , Diterpenos/química , Diterpenos/farmacología , Furanos/química , Furanos/farmacología , Humanos , Espectroscopía de Resonancia Magnética , Magnoliopsida/química , Mycobacterium tuberculosis/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Spodoptera , Células Tumorales Cultivadas , Células VeroRESUMEN
Eleven bioxanthracenes and two monomers, six novel in nature, were isolated from the insect pathogenic fungus Cordyceps pseudomilitaris BCC 1620. Growth optimization of the strain led to the improvement of bioxanthracenes production. The bioxanthracenes were evaluated for their antimalarial activity and cytotoxicity.
Asunto(s)
Antracenos/aislamiento & purificación , Antimaláricos/aislamiento & purificación , Antimaláricos/farmacología , Hypocreales/clasificación , Hypocreales/metabolismo , Animales , Antracenos/metabolismo , Antracenos/farmacología , Antimaláricos/metabolismo , Línea Celular , Fermentación , Humanos , Hypocreales/patogenicidad , Concentración 50 Inhibidora , Insectos/microbiología , Pruebas de Sensibilidad Microbiana , Plasmodium falciparum/efectos de los fármacos , Pruebas de ToxicidadRESUMEN
Structures of eleven bioxanthracenes (1 approximately 11) and two monomers (12 and 13), isolated from the insect pathogenic fungus Cordyceps pseudomilitaris BCC 1620, were elucidated. The structure, including the axial stereochemistry, of one of the major symmetrical dimers (1) was determined by X-ray crystallographic analysis, while the stereochemistries of the other isomers were deduced by chemical conversions and spectroscopic means.
Asunto(s)
Antracenos/química , Hypocreales/química , Animales , Cristalografía por Rayos X , Dimerización , Hypocreales/patogenicidad , Insectos/microbiología , Espectroscopía de Resonancia Magnética , Estructura Molecular , EstereoisomerismoRESUMEN
Racemosol and demethylracemosol, together with their possible biogenetic precursors, preracemosol A and preracemosol B, were isolated from the roots of Bauhinia malabarica Roxb. While only racemosol and demethylracemosol exhibited cytotoxicity against KB and BC cell lines, all four compounds exhibited moderate antimalarial activity.
Asunto(s)
Antimaláricos/metabolismo , Bibencilos/metabolismo , Rosales/química , Terpenos/metabolismo , Animales , Antimaláricos/química , Antimaláricos/farmacología , Bibencilos/química , Raíces de Plantas/química , Plasmodium falciparum/efectos de los fármacos , Análisis Espectral , Terpenos/químicaAsunto(s)
Antineoplásicos Fitogénicos/química , Benzofuranos , Disacáridos/química , Plantas Medicinales/química , Sesquiterpenos , Compuestos de Espiro/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Disacáridos/aislamiento & purificación , Disacáridos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Estructura Molecular , Raíces de Plantas/química , Compuestos de Espiro/aislamiento & purificación , Compuestos de Espiro/farmacología , Células Tumorales CultivadasRESUMEN
Bioassay-guided fractionation of the extract from the wood-decayed fungus Xylaria sp. BCC 1067 led to the isolation of five antiplasmodial compounds, (-)-depudecin, (+)-phaseolinone, (+)-phomenone, 19,20-epoxycytochalasin Q, and (E)-methyl 3-(4-methoxyphenoxy)propenoate. These structures were elucidated using spectroscopic methods, especially NMR analysis.
Asunto(s)
Antimaláricos/aislamiento & purificación , Antineoplásicos/aislamiento & purificación , Ascomicetos/química , Alcadienos/química , Alcadienos/aislamiento & purificación , Alcadienos/farmacología , Animales , Antimaláricos/química , Antimaláricos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Cromatografía Líquida de Alta Presión , Compuestos Epoxi/química , Compuestos Epoxi/aislamiento & purificación , Compuestos Epoxi/farmacología , Alcoholes Grasos/química , Alcoholes Grasos/aislamiento & purificación , Alcoholes Grasos/farmacología , Humanos , Espectroscopía de Resonancia Magnética , Naftoles/química , Naftoles/aislamiento & purificación , Naftoles/farmacología , Plasmodium falciparum/efectos de los fármacos , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/farmacología , Células Tumorales CultivadasRESUMEN
Antimalarial activity-guided study of the aerial parts of Artocarpus integer led to the isolation of the prenylated stilbene, trans-4-(3-methyl-E-but-1-enyl)-3,5,2',4'-tetrahydroxystilbene with an EC50 of 1.7 micrograms/ml against Plasmodium falciparum in culture. The known stilbenes, trans-4-isopentenyl-3,5,2',4'-tetrahydroxystilbene and 4-methoxy-2,2-dimethyl-6-(2-(2,4-dihydroxy)phenyl-trans-ethenyl)chromene , were also isolated. Structures of these compounds were deduced on the basis of their spectral data.
Asunto(s)
Antimaláricos/aislamiento & purificación , Plantas Medicinales/química , Estilbenos/aislamiento & purificación , Animales , Antimaláricos/química , Antimaláricos/farmacología , Espectroscopía de Resonancia Magnética , Estructura Molecular , Plasmodium falciparum/efectos de los fármacos , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
The nature of the interactions between Plasmodium falciparum dihydrofolate reductase (pfDHFR) and antimalarial antifolates, i.e., pyrimethamine (Pyr), cycloguanil (Cyc) and WR99210 including some of their analogues, was investigated by molecular modeling in conjunction with the determination of the inhibition constants (Ki). A three-dimensional structural model of pfDHFR was constructed using multiple sequence alignment and homology modeling procedures, followed by extensive molecular dynamics calculations. Mutations at amino acid residues 16 and 108 known to be associated with antifolate resistance were introduced into the structure, and the interactions of the inhibitors with the enzymes were assessed by docking and molecular dynamics for both wild-type and mutant DHFRs. The Ki values of a number of analogues tested support the validity of the model. A 'steric constraint' hypothesis is proposed to explain the structural basis of the antifolate resistance.
Asunto(s)
Resistencia a Medicamentos , Antagonistas del Ácido Fólico/farmacología , Pirimetamina/farmacología , Tetrahidrofolato Deshidrogenasa/efectos de los fármacos , Triazinas/farmacología , Secuencia de Aminoácidos , Antagonistas del Ácido Fólico/química , Modelos Moleculares , Datos de Secuencia Molecular , Estructura Molecular , Proguanil , Pirimetamina/química , Homología de Secuencia de Aminoácido , Tetrahidrofolato Deshidrogenasa/química , Triazinas/químicaRESUMEN
Activity guided fractionation of extracts from Clausena harmandiana have led to the identification of four known compounds, heptaphylline (1), clausine K (2), dentatin (5), and clausarin (6). All these compounds, except clausine K (2), exhibited antiplasmodial activity against Plasmodium falciparum. While the new dimethylated derivative 4, derived from 2, showed no antiplasmodial activity, the monomethylated product 3 (clausine H) exhibited activity comparable to that observed for compounds 1 and 5.
Asunto(s)
Antimaláricos/farmacología , Carbazoles/farmacología , Cumarinas/farmacología , Plantas/química , Plasmodium falciparum/efectos de los fármacos , Animales , Antimaláricos/química , Antimaláricos/aislamiento & purificación , Carbazoles/química , Carbazoles/aislamiento & purificación , Cumarinas/química , Cumarinas/aislamiento & purificación , HumanosRESUMEN
Bioassay-guided fractionation of the crude extract from the insect pathogenic fungus Paecilomyces tenuipes BCC 1614 led to the isolation and identification of two antimycobacterial and antiplasmodial cyclodepsipeptides, beauvericin and beauvericin A.
Asunto(s)
Antimaláricos/aislamiento & purificación , Antituberculosos/aislamiento & purificación , Ascomicetos/química , Insectos/microbiología , Péptidos Cíclicos/aislamiento & purificación , Animales , Antimaláricos/química , Antimaláricos/farmacología , Antituberculosos/química , Antituberculosos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis/efectos de los fármacos , Péptidos Cíclicos/química , Péptidos Cíclicos/farmacologíaRESUMEN
Research on natural products provides not only knowledge and understanding of living organisms but chemical entities obtained from bioresources can also be used as structural models for further development in the various fields, notably in the agricultural and pharmaceutical sciences. Selected examples on the scientific aspects of traditional usage of bioresources are described.
Asunto(s)
Medicina Tradicional , Farmacología/métodos , Agroquímicos/aislamiento & purificación , TailandiaRESUMEN
Bioassay-guided fractionation of an extract from the fungus Myrothecium verrucaria BCC 112 resulted in the first isolation of roridin E acetate (5) from nature together with four common macrocyclic trichothecene isomers (1-4). Trichothecenes 1-5, while known as mycotoxins, were evaluated for their high antimalarial activity.