Alcaloïdes de Papaver arachnoïdeum (synthèse et évaluation biologique d'analogues structuraux de produits naturels à visées cytotoxique et antibactérienne en série benzophénanthrolines et benzothiophènes=)

Ce travail porte d une part sur l extraction, l isolement et l identification des alcaloïdes d un pavot endémique de Turquie, Papaver arachnoïdeum Kadereit, d autre part, sur la synthèse d analogues de produits naturels de série benzothieno[3,2-f][1]benzopyrane, à potentialités antimicrobiennes et antifongiques, et de série benzo[c]phénanthrolines, à visée antitumorale. Dans la première partie, l étude d extraits alcaloïdiques de Papaver arachnoïdeum collectés dans deux régions différentes de Turquie est réalisée. Cinq alcaloides sont isolés. Il s agit d une aporphine, la roemerine, d une oxoaporphine, la liriodénine et de trois proaporphines la mécambrine, la roemeronine et le déhydromecambrinol B. La configuration absolue de ces trois derniers dérivés est déterminée. Ces résultats sont discutés des points de vue biogénétique et chimiotaxonomique. La deuxième partie porte sur la synthèse de nouveaux dérivés de série benzothieno[3,2-f][1]benzopyrane, comportant un motif chromène rencontré dans de nombreuses substances naturelles fusionné avec un thiophène, pharmacophore connu comme support d activités antifongiques et antibactériennes. L étape clé de la synthèse est un réarrangement thermique de type Claisen d un éther propargylique du 2-hydroxydibenzothiopène. La double liaison du cycle pyrannique a été fonctionnalisée par oxydation en diols et diacétates cis et trans. Les activités antibactérienne, antifongique et antiuberculeuse des composés ont été évaluées. La dernière partie traite de la synthèse de nouveaux composés de série benzo[c]phénanthroline. La structure de ces molécules s inspire de celle d alcaloïdes isolés de Rutaceae appartenant au genre Zanthoxylum, comme la nitidine et la fagaronine qui présentent des activités cytotoxiques intéressantes. La substitution des noyaux benzo[c][1,7] et [1,8] phénanthroline par différentes chaînes de type dialkylaminoalkyle permet d accroître la solubilité dans des solvants biocompatibles et d améliorer l activité cytotoxique par rapport aux composés.This work describes the extraction, the isolation and the identification of the alkaloids of Papaver arachnoïdeum Kadereit, a poppy species endemic from Turkey, on the one hand, and the synthesis of natural products analogues in the benzothieno[3,2-f][1]benzopyran and benzo[c]phenanthroline series, with potential antimicrobial and anticancer activities, respectively, on the other hand. The alkaloid extracts of Papaver arachnoïdeum, collected in two different regions of Turkey, led to the isolation of five compounds. : an aporphine, roemerine, an oxoaporphine, liriodenine, and three proaporphines whose absolute configurations have been determined : mecambrine, roemeronine, dihydromecambrinol B. These results are discussed from both biogenetic and chemotaxonomic points of view. The second part deals with the synthesis of new benzothieno[3,2-f][1]benzopyran derivatives, whose structure include a chromene unit, encountered in numerous natural compounds, fused onto a thiophene present in several antifungal and antibacterial structures. The key-step of the synthesis of the lead compound was the thermal Claisen rearrangement of a propargyl ether derived from 2-hydroxydibenzothiopene. The pyran double bond was further converted into the corresponding cis and trans diols and diacetates. The compounds were tested in vitro for their antibacterial, antifungal, and antiubercular activities. In the last part, the syntheses of new benzo[c]phenanthroline derivatives are described. The structures of these novel compounds relate to those of antiproliferative alkaloids isolated from Rutaceae species belonging to the genus Zanthoxylum, such as nitidine and fagaronine. Substitution of the benzo[c][1,7] and [1,8]phenanthroline basic core by various dialkylaminoalkyl substituents gave access to new compounds exhibiting better cytotoxic activities associated with increased solubility in biocompatible solvents, when compared with the parent compoundsPARIS-BIUP (751062107) / SudocSudocFranceF

Cytotoxic activities of some Turkish medicinal plants against HeLa cells in vitro

The aim of this study was to characterize the biological activities of traditionally used medicinal plants generally collected from Kirklareli, Turkey against cancer. We evaluated the cytotoxic activities of different extracts prepared from Urtica dioica L. 1, Achillea millefolium L. ssp. pannonica 2, Malva sylvestris L. 3, Stachys cretica L. ssp. mersinaea (Boiss.) Rechf.f. (endemic) 4, Melissa officinalis L. 5, Cotinus coggyria Scop. 6, Sorbus aucuparia L. 7, and Plantago major L. ssp. major 8 species. Ethanol (a), petroleum ether (b), dichloromethane (c) and ethyl acetate (d) fractions of each plant material were obtained. Cytotoxicity in HeLa cells was evaluated using the MTT assay. Among the extracts, 7c, 2b, 6d, 7d, 7a, 2c, and 3b showed potent cytotoxic activity with IC50 values of less than 50 mu g/mL, in descending order. Dichloromethane extract of S. aucuparia is considered highly active, with IC50 of 15 03 (mean +/- SD) mu g/mL. The extracts 8a and 8b also showed good cytotoxic activity. According to the results, dichloromethane extracts of S. aucuparia had the most potent anticancer activity in HeLa cells and should be considered as a potential clinical agent. The results support the ethnomedical claims for these species and suggest further in vitro and/or in vivo studies of the active extracts

Cytotoxic activities of some Turkish medicinal plants against HeLa cells <em>in vitro</em>

43-49The aim of this study was to characterize the biological activities of traditionally used medicinal plants generally collected from Kırklareli, Turkey against cancer. We evaluated the cytotoxic activities of different extracts prepared from Urtica dioica L. 1, Achillea millefolium L. ssp. pannonica 2, Malva sylvestris L. 3, Stachys cretica L. ssp . mersinaea (Boiss.) Rechf.f. (endemic) 4, Melissa officinalis L. 5, Cotinus coggyria Scop. 6, Sorbus aucuparia L. 7 , and Plantago major L. ssp. major 8 species. Ethanol (a), petroleum ether (b), dichloromethane (c) and ethyl acetate (d) fractions of each plant material were obtained. Cytotoxicity in HeLa cells was evaluated using the MTT assay. Among the extracts, 7c, 2b, 6d, 7d, 7a, 2c, and 3b showed potent cytotoxic activity with IC50 values of less than 50 μg/mL, in descending order. Dichloromethane extract of S. aucuparia is considered highly active, with IC50 of 15±03 (mean ± SD) μg/mL. The extracts 8a and 8b also showed good cytotoxic activity. According to the results, dichloromethane extracts of S. aucuparia had the most potent anticancer activity in HeLa cells and should be considered as a potential clinical agent. The results support the ethnomedical claims for these species and suggest further in vitro and/or in vivo studies of the active extracts

Antioxidant, anti-inflammatory, acetylcholinesterase and thioredoxin reductase inhibitory activities of nine selected Turkish medicinal plants

Ethyl acetate, methanol, dichloromethane, petroleum ether and water extracts of nine selected plant species, which are commonly used as herbal medicines for anticancer and anti-inflammatory purposes in Turkey, were evaluated for their total phenolic and flavonoid contents and in vitro antioxidant potency with a thiobarbituric acid assay using the lipid peroxidation of phosphatidylcholine liposomes, DPPII and ferric ion reducing antioxidant power assays. Inhibitory activity against cyclooxygenase (COX) was used to evaluate the anti-inflammatory activities of the extracts. As thioredoxin reductase (TrxR) has emerged as a new target for anticancer drug development, the extracts were investigated for their inhibitory activities on TrxR. The ability of the extracts to inhibit acetylcholinesterase (AChE), which is a target for cholinesterase inhibitors, used for the symptomatic treatment of Alzheimer's disease, was also examined. The results showed that the extracts of C. coggygria and M. officinalis subsp. officinalis are the. most effective hydrogen and electron donors and contained the highest amounts of phenolic compounds; thus, they can be considered the best antioxidants among the nine plants selected for the study. All the plants showed inhibitory effects against AChE, COX-1 and COX-2, therefore may be of potential therapeutic interest for the treatment of neurodegenerative and inflammatory disorders. It was found that M. officinalis subsp. officinalis, C. coggyria, S. aucuparia and P. major subsp. major have a strong inhibitory effect on TrxR by up to 99 %, highlighting their potential as preventive therapeutics for cancer. This study confirmed the use of these plants in folk medicine as anti-inflammatory and anticancer agents

Synthesis and Antimicrobial Activities of Some Sulphur Containing Chromene Derivatives

A series of 3,3-dimethyl-3Hbenzothieno[3,2-f][1]-benzopyran analogues modified at the pyran 1,2-double bond were synthesized. The corresponding dihydro and (+/-)-cis-diol derivatives were converted into diacetate and cyclic carbonate upon acylation. The title compounds were characterized by spectroscopic analysis and screened for their antimicrobial activity in vitro

Antioxidant, anti-inflammatory, acetylcholinesterase and thioredoxin reductase inhibitory activities of nine selected Turkish medicinal plants

553-561Ethyl acetate, methanol, dichloromethane, petroleum ether and water extracts of nine selected plant species, which are commonly used as herbal medicines for anticancer and anti-inflammatory purposes in Turkey, were evaluated for their total phenolic and flavonoid contents and in vitro antioxidant potency with a thiobarbituric acid assay using the lipid peroxidation of phosphatidylcholine liposomes, DPPH&middot; and ferric ion reducing antioxidant power assays. Inhibitory activity against cyclooxygenase (COX) was used to evaluate the anti-inflammatory activities of the extracts. As thioredoxin reductase (TrxR) has emerged as a new target for anticancer drug development, the extracts were investigated for their inhibitory activities on TrxR. The ability of the extracts to inhibit acetylcholinesterase (AChE), which is a target for cholinesterase inhibitors, used for the symptomatic treatment of Alzheimer&rsquo;s disease, was also examined. The results showed that the extracts of C. coggygria and M. officinalis subsp. officinalis are the most effective hydrogen and electron donors and contained the highest amounts of phenolic compounds; thus, they can be considered the best antioxidants among the nine plants selected for the study. All the plants showed inhibitory effects against AChE, COX-1 and COX-2, therefore may be of potential therapeutic interest for the treatment of neurodegenerative and inflammatory disorders. It was found that M. officinalis subsp. officinalis, C. coggyria, S. aucuparia and P. major subsp. major have a strong inhibitory effect on TrxR by up to 99 %, highlighting their potential as preventive therapeutics for cancer. This study confirmed the use of these plants in folk medicine as anti-inflammatory and anticancer agents

Essential Oil Composition, Antimicrobial and Cytotoxic Activities of Two Endemic Stachys cretica Subspecies (Lamiaceae) from Turkey

The chemical compositions of the water-distilled essential oil of Stachys cretica ssp. lesbiaca Rech. fil. and S. cretica ssp. trapezuntica Rech. fil. were determined by GC and GC MS. Altogether 63 compounds were identified. The sesquiterpene hydrocarbon, germacrene D (20.3% and 12.9% respectively) was the main component identified in both oils. Furthermore, ethanol, light petroleum, dichloromethane, ethyl acetate and n-butanol extracts prepared from the aerial parts of the plants were tested for their antimicrobial activities against six bacterial strains and the yeast Candida albicans. The extracts exhibited no antibacterial activity, but the light petroleum and n-butanolic fractions showed low antifungal activities. Crude ethanolic extracts of the two subspecies were tested for their ability to inhibit the growth of HL-60 and Ishikawa human tumor cell lines. The IC50 values were 100 mu g/mL for the HL-60 cell line and 200 mu g/mL for the Ishikawa cell line

Chemical composition of the essential oil and antioxidant activity of methanolic extracts from fruits and flowers of Hypericum lydium Boiss.

This study was conducted to evaluate the essential oil composition and antioxidant activity of methanolic extracts from fruits and flowers of Hypericum lydium Boiss., a wild growing species of the Turkish flora. The antioxidant activities were determined through several biochemical assays. Both extracts showed an inhibitory effect against the formation of TBARS in a phosphatidylcholine liposome model system, moderate scavenging effect on DPPH center dot and superoxide radicals, prominent reducing power and inhibitory effect on deoxyribose degradation in both the nonsite and site-specific assay, but a greater hydroxyl radical scavenging activity was observed in the non-site specific assay, suggesting that the extracts were better at scavenging hydroxyl radicals than at chelating iron. Correlation analysis indicated that there was a linear relationship between antioxidant potency, free-radical scavenging activity, reducing power and the content of flavonoids of fruits and flowers extracts. The essential oils obtained by hydrodistillation were analyzed by GC and GC-MS. In total forty-three compounds were identified. The most abundant components were monoterpenes hydrocarbons represented principally by alpha-pinene. The tested oil showed no antioxidant activity. (C) 2011 Elsevier B.V. All rights reserved