RESUMEN
Natural products frequently exert pharmacological activities. The present review gives an overview of the ethnobotany, phytochemistry and pharmacology of the Cedrus genus, e.g. cytotoxic, spasmolytic immunomodulatory, antiallergic, anti-inflammatory and analgesic activities. Cancer patients frequently seek remedies from traditional medicinal plants that are believed to exert less side effects than conventional therapy with synthetic drugs. A long-lasting goal of anti-cancer and anti-microbial therapy research is to find compounds with reduced side effects compared to currently approved drugs. In this respect, Cedrus species might be of interest. The essential oil isolated from Cedrus libani leaves may bear potential for drug development due to its high concentrations of germacrene D and ß-caryophyllene. The essential oils from Cedrus species also show bioactivity against bacteria and viruses. More preclinical analyses (e.g. in vivo experiments) as well as clinical trials are required to evaluate the potential of essential oils from Cedrus species for drug development.
Asunto(s)
Cedrus/química , Aceites Volátiles/química , Aceites Volátiles/farmacología , Plantas Medicinales/química , Antiinfecciosos/farmacología , Antiinflamatorios , Antineoplásicos Fitogénicos/farmacología , Humanos , Fitoquímicos/análisis , Fitoquímicos/farmacología , Hojas de la Planta/química , Sesquiterpenos Policíclicos , Sesquiterpenos/análisisRESUMEN
The frequent failure of standard cancer chemotherapy requires the development of novel drugs capable of killing otherwise drug-resistant tumors. Here, we have investigated a chloroform extract of Laurus nobilis seeds. Fatty acids and 23 constituents of the volatile fraction were identified by gas chromotography/flame ionization detection (GC/FID) and gas chromatography/mass spectrometry (GC/MS), in good agreement with (1)H NMR (nuclear magnetic resonance) spectrum. Multidrug-resistant P-glycoprotein-expressing CEM/ADR5000 leukemia cells were hypersensitive (collaterally sensitive) toward this extract compared to drug-sensitive CCRF-CEM cells, whereas CEM/ADR5000 cells were 2586-fold resistant to doxorubicin as control drug. Collateral sensitivity was verified by measurement of apoptotic cells by flow cytometry. The log10IC50 values of 3 compounds in the extract (limonene, eucalyptol, oleic acid) did not correlate with mRNA expression of the P-glycoprotein-coding ABCB1/MDR1 gene and accumulation of the P-glycoprotein substrate rhodamine in the NCI panel of tumor cell lines. A microarray-based profile of 20 genes predicted resistance to doxorubicin and 7 other anticancer drugs involved in the multidrug resistance phenotype but not to limonene, eucalyptol and oleic acid. In conclusion, our results show that Laurus nobilis seed extract is suitable to kill multidrug-resistant P-glycoprotein expressing tumor cells.
Asunto(s)
Resistencia a Antineoplásicos , Laurus/química , Extractos Vegetales/farmacología , Semillas/química , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/farmacología , Cromatografía de Gases y Espectrometría de Masas , Humanos , Leucemia/patologíaRESUMEN
A set of 6-substituted quinolone nucleosides linked to aniline or phenol via N or O heteroatom-bridges presenting new compounds were synthesized by palladium-catalyzed Buchwald-Hartwig cross-coupling reactions. 6-Bromoquinolone nucleoside precursors, being protected by either benzoyl or TBDMS protecting groups on the ribose moiety, were subjected to different Buchwald-Hartwig conditions as the key step. Defined deprotection steps led, in good yields, to the final target compounds that carry, in position 3, either ester, acid, or amide functions. Thus, a series of novel quinolone nucleoside derivatives was obtained via a convergent synthesis route. Biological tests in human chronic myelogenous leukemia K562 cells exerted an efficient antiproliferative activity for two of them without induction of differentiation. These novel nucleosides deserve further experiments to determine their antiproliferative effects on other CML cell lines.
Asunto(s)
Antineoplásicos/farmacología , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Nucleósidos/farmacología , Quinolonas/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Humanos , Células K562 , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Nucleósidos/síntesis química , Nucleósidos/química , Quinolonas/síntesis química , Quinolonas/química , Relación Estructura-ActividadRESUMEN
Juniperus excelsa fruit essential oil as well as J. oxycedrus, Cedrus libani, and Pinus pinea wood essential oils have been obtained with yields between 2.2 ± 0.3â% to 3.4 ± 0.5â% and analyzed by gas chromatography. Sesquiterpenes mainly characterized C. libani and J. oxycedrus essential oils, while in P. pinea and J. excelsa, monoterpenes were the most abundant compounds. In J. oxycedrus, cis-calamenene (7.8â%), cuparene (3.8â%), and cis-thujopsenal (2.0â%) have been detected for the first time. The cytotoxic activity of these essential oils against drug-sensitive CCRF-CEM and multidrug-resistant P-glycoprotein-expressing CEM/ADR5000 leukemia cells has been investigated (IC50 values: 29.46 to 61.54 µg/mL). Remarkably, multidrug-resistant CEM/ADR5000 cells did not reveal cross-resistance, indicating that these essential oils might be useful to treat otherwise drug-resistant and refractory tumors.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Leucemia/tratamiento farmacológico , Aceites Volátiles/química , Fitoterapia , Plantas Medicinales/química , Células Tumorales Cultivadas/efectos de los fármacos , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Cedrus/química , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Frutas/química , Humanos , Juniperus/química , Líbano , Monoterpenos/aislamiento & purificación , Aceites Volátiles/farmacología , Pinus/química , Sesquiterpenos/aislamiento & purificación , Madera/químicaRESUMEN
There are four kinds of Cedar: Cedrus libani naturally occurring in Lebanon, Syria and Turkey, Cedrus atlantica in Morocco and Algeria, Cedrus brevefolia in Cyprus Island and Cedrus deodara which is distributed in Himalayan Mountains. Wood essential oils obtained from C. libani, C. atlantica and C. deodara were tested for the inhibition of K562 cell proliferation and for the induction of erythroid differentiation. The wood essential oils of C. libani, C. atlantica and C. deodara inhibited the proliferation of the K562 cell line exhibiting IC(50) values 23.38 ± 1.7, 59.37 ± 2.6 and 37.09 ± 1.4 µg mL(-1), respectively. Meanwhile, C. libani wood oils induced a percentage of erythroid differentiation of 15 ± 2% at concentration 5 µg mL(-1). Cedrus deodara wood oil indicated a percentage of erythroid differentiation of 20 ± 2% at concentration 25 µg mL(-1) and C. atlantica wood oils showed a percentage of erythroid differentiation of 12 ± 1.8% at concentration 10 µg mL(-1).
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Cedrus/química , Aceites Volátiles/farmacología , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Concentración 50 Inhibidora , Células K562/efectos de los fármacos , Madera/químicaRESUMEN
The antioxidant and antiproliferative activities of the essential oils from Laurus nobilis leaves and seeds in relation to their composition were analysed. The most abundant components of the leaf essential oil were 1,8-cineole, 1-p-menthen-8-ethyl acetate, linalool and sabinene, while the seed oil was characterised by ß-ocimene, 1,8-cineole, α-pinene and ß-pinene as main constituents. Both seed and leaf essential oils exhibited a scavenging effect on the DPPH radical, with IC50 values of 66.1 and 53.5 µg mL⻹, respectively. The leaf essential oil showed the strongest antioxidant activity in the ß-carotene/linoleic acid system, with an IC50 value of 35.6 µg mL⻹ after 30 min of incubation. Both leaf and seed oils inhibited proliferation of the K562 tumour cell line with IC50 values of 95 and 75 µg mL⻹, respectively. The L. nobilis leaf oil showed a percentage of erythroide differentiation of 15% at a concentration of 10 µg mL⻹. A value of 12% was found for the seed essential oil at a concentration of 50 µg mL⻹. When the oils were added to a suboptimal concentration of the commercial drug, cytosine arabinoside, a clear synergic effect was observed.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Laurus/química , Aceites Volátiles/química , Aceites Volátiles/farmacología , Hojas de la Planta/química , Semillas/química , Compuestos de Bifenilo/química , Línea Celular Tumoral , Humanos , Picratos/químicaRESUMEN
The aim of this work was to examine the chemical composition and antiproliferative activity of Salvia leriifolia Benth. and Salvia acetabulosa L. oils. S. leriifolia oil was characterized by 50 components, whereas 19 components were identified in S. acetabulosa. S. leriifolia oil was characterized by camphor (10.5%), 1,8-cineole (8.6%), camphene (6.2%), and alpha-pinene (4.7%). alpha-Pinene (52.3%), 1,8-cineole (27.7%), and camphor (6.7%) were the major components in S. acetabulosa oil. Both oils exerted a strong antiproliferative activity comparing with vinblastine against COR-L23 with 50% inhibitory concentration (IC(50)) values of 7.5 and 6.5 microg/mL for S. leriifolia and S. acetabulosa, respectively. Salvia oils showed an interesting activity also on C32 (IC(50) = 6.3 and 9.1 microg/mL for S. acetabulosa and S. leriifolia, respectively). S. acetabulosa was also found to possess cytotoxic activity against renal adenocarcinoma (IC(50) = 6.8 microg/mL). The results clearly showed that for both Salvia species the antiproliferative activity could not be related to the major abundant compounds. Consequently, the minor components may be involved in some type of synergism with the other active compounds.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias Renales/tratamiento farmacológico , Aceites Volátiles/uso terapéutico , Fitoterapia , Extractos Vegetales/uso terapéutico , Salvia/química , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Sinergismo Farmacológico , Humanos , Concentración 50 Inhibidora , Aceites Volátiles/química , Aceites Volátiles/farmacología , Componentes Aéreos de las Plantas , Extractos Vegetales/química , Extractos Vegetales/farmacologíaRESUMEN
AIM OF THE STUDY: In recent years the use of medicinal plants has been growing worldwide and this is particularly true in Lebanon. In the present investigation we report the inhibitory activity against digestive enzymes related to diabetes and angiotensin converting enzyme (ACE) of extracts of nine plant species collected in Lebanon, where they have a traditional use against diabetes. MATERIALS AND METHODS: In order to evaluate if the extraction procedure could influence the activity we decided to perform different extractions with methanol, n-hexane and chloroform of Calamintha origanifolia, Satureja thymbra, Prangos asperula, Sideritis perfoliata, Asperula glomerata, Hyssopus officinalis, Erythraea centaurium, Marrubium radiatum and Salvia acetabulosa and test each of them. RESULTS AND CONCLUSIONS: Marrubium radiatum and Salvia acetabulosa methanol extracts exerted the highest activity against alpha-amylase (IC(50) 61.1 and 91.2 microg/ml, respectively) and alpha-glucosidase (IC(50) 68.8 and 76.9 microg/ml, respectively). The same extracts exhibited a strong inhibitory activity against ACE with IC(50) of 72.7 and 52.7 microg/ml, respectively. The results support the traditional use of some the species examined.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Diabetes Mellitus/tratamiento farmacológico , Extractos Vegetales/farmacología , Plantas Medicinales/química , Inhibidores de la Enzima Convertidora de Angiotensina/aislamiento & purificación , Diabetes Mellitus/fisiopatología , Concentración 50 Inhibidora , Líbano , Medicina Tradicional , alfa-Amilasas/efectos de los fármacos , alfa-Amilasas/metabolismo , alfa-Glucosidasas/efectos de los fármacos , alfa-Glucosidasas/metabolismoRESUMEN
The chemical composition of the essential oils of Laurus nobilis, Juniperus oxycedrus ssp. oxycedrus, Thuja orientalis, Cupressus sempervirens ssp. pyramidalis, Pistacia palaestina, Salvia officinalis, and Satureja thymbra was determined by GC/MS analysis. Essential oils have been evaluated for their inhibitory activity against SARS-CoV and HSV-1 replication in vitro by visually scoring of the virus-induced cytopathogenic effect post-infection. L. nobilis oil exerted an interesting activity against SARS-CoV with an IC(50) value of 120 microg/ml and a selectivity index (SI) of 4.16. This oil was characterized by the presence of beta-ocimene, 1,8-cineole, alpha-pinene, and beta-pinene as the main constituents. J. oxycedrus ssp. oxycedrus oil, in which alpha-pinene and beta-myrcene were the major constituents, revealed antiviral activity against HSV-1 with an IC(50) value of 200 microg/ml and a SI of 5.
Asunto(s)
Antivirales/farmacología , Herpesvirus Humano 1/efectos de los fármacos , Juniperus/química , Laurus/química , Aceites Volátiles/química , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/efectos de los fármacos , Animales , Antivirales/química , Antivirales/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Chlorocebus aethiops , Cromatografía de Gases y Espectrometría de Masas , Concentración 50 Inhibidora , Líbano , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Aceites Volátiles/farmacología , Estructuras de las Plantas/química , Células VeroRESUMEN
The essential oils obtained from different officinal plants of Lebanon, belonging to the Magnoliophyta division, have been tested for their antiproliferative activity on human erythroleukemic K562 cells. Satureja montana showed the most interesting biological activity in inhibiting the cell growth and inducing erythroid differentiation of K562 cells. The essential oil of Satureja montana was therefore analyzed using a GC/MS (gas chromatography/mass spectrometry) system in order to identify the major constituents and compare them with analysis performed on Satureja hortensis. We demonstrated that the essential oil composition varied with the species, the major constituent of Satureja hortensis being carvacrol (50.61%) and that of Satureja montana being alpha-terpineol (12.66%). In order to identify molecules possibly responsible for the biological activity, commercially available derivatives have been assayed on the K562 cell line. Satureja montana essential oil displayed different natural derivatives characterized by higher activity than those present in Satureja hortensis. The common active principles are alpha-pinene, gamma-terpinene, 4-terpineol, alpha-terpineol, tau-cadinene, tau-cadinol and caryophyllene. Both caryophyllene and alpha-terpineol showed important antiproliferative effects on K562 cells.