Activity Guided Fractionation of Arum italicum Miller Tubers and the LC/MS-MS Profiles

WOS: 000411767600006In this study, the polar extract of Arum italicum Miller tubers was fractionated by ` biological activity guided fractionation' method. MCF-7 (human breast adenocarcinoma) and A549 (non-small lung cancer) cancer cell lines were used to screen cytotoxic activity. Possible antiproliferative and apoptotic effects of each subfraction were evaluated by in vitro. As a result, E2 were cytotoxic against A549 cell lines while E3 and E6 showed good cytotoxic activities against both cancer cell lines. These three subfractions showed apoptotic and antiproliferative effects comparable with positive control. The chemical composition of each subfraction was determined by LC/MS-MS. Hydroxycinnamic acid derivatives, lignans and glycosides, hydroxycinnamic acidspermidine conjugates and oxylipins identified in subfractions were major secondary metabolites.PhD thesis project of Hale Gamze Agalar [BAP-1206S100]; Commision of Scientific Research Projects of Anadolu University, Eskisehir, Turkey [BAP-1705S304]This work was supported as a PhD thesis project of Hale Gamze Agalar (BAP-1206S100) and financially supported by Research Incentive Projects (BAP-1705S304) by Commision of Scientific Research Projects of Anadolu University, Eskisehir, Turkey

Arum italicum Miller tuber extracts: Evaluation of synergistic activities with ciprofloxacin against some pathogens

Antibiotic misuse or overuse leads antibiotic resistance. Antibiotic resistant bacteria infections cause significant clinical problem. Recently, antibiotic resistant bacteria numbers have increased, this situation has become a global public health treat. To achieve these problems, development of new antibacterial compounds is still popular among researchers. The focus on natural compounds/plant extracts in combination with antibiotics increase their activities and decrease the doses of antibiotics and their side effects. Despite known as poisonous, Arum italicum Miller is used as food and/or is used for the treatment such ailments as furuncle, eczema, peptic ulcer, wounds, etc. This interesting species was found as anticancer, cytotoxic, apoptotic agent against some human cancers. In the present study, the fractions of A. italicum tuber extract against human pathogens (Pseudomonas aeruginosa ATCC 27853, Bacillus cereus NRRL B-3711, Staphylococcus aureus ATCC 6538) were evaluated for their antibacterial activities by microdilution method. Each fraction was combined with ciprofloxacin and their synergistic activities were tested by checkerboard method. The MIC (minimum inhibitory concentrations) and FICI (fractional inhibitory concentration indexes) values were calculated. Totally, seven synergic interactions, ten additive interactions, and four indifferent interactions of tested fractions with ciprofloxacin were found

Arum italicum miller üzerinde farmakognozik araştırmalar

Tez (doktora) - Anadolu ÜniversitesiAnadolu Üniversitesi, Sağlık Bilimleri Enstitüsü, Farmakognozi Anabilim DalıKayıt no: 3223Günümüzde kardiyovasküler hastalıklardan sonra en çok ölüme neden olan hastalıkların başında kontrolsüz hücre çoğalması ile karakterize kanser gelmektedir. Kanser tedavisinde kullanılan ilaçlar kanserli hücreleri öldürmenin yanında sağlıklı hücrelere de sitotoksik etki göstermektedir. Hem kanserin oluşum mekanizmalarının kompleks oluşu hem de tedavide kullanılan ilaçların terapötik indekslerinin düşük oluşu nedeniyle tedavide kullanılabilecek yeni maddelerin araştırılması önemini korumaktadır. Bu nedenle başta doğal kaynaklı maddeler olmak üzere çeşitli maddelerin olası antikanser etkileri araştırılmaya devam etmektedir. Halk arasında kanserden korunma amacıyla yumruları tüketilen ve 'yılan yastığı' olarak bilinen Arum italicum Miller (Araceae) bitkisi dikkat çekmektedir. A. italicum bitkisi toksik olarak bilinmesine rağmen halk arasında gıda olarak ve tedavi amaçlı kullanılmaktadır. Kaynaklara göre, bazı yörelerde yumrulardan hazırlanan dekoksiyonun dâhilen kanser ve kadın hastalıklarında; balla karıştırılan dilimlenmiş yumruların ise peptik ülser ve kansere karşı kullanıldığı bilinmektedir. fitokimyasal araştırmalarda, saponin, alkaloit, steroidal bileşikler, neolignan ve furan türevi lignanlar gibi biyolojik olarak aktif sekonder metabolitleri A. italicum'dan tanımlanmıştır. Bu bilgilerden hareketle, yumrulardan hazırlanan ekstre 'biyolojik aktivite yönlendirmeli fraksiyonlama' yöntemi kullanılarak fraksiyonlanmış ve meme (MCF-7) ve akciğer (A549) kanser hücre hatları sitotoksik aktivitenin araştırılmasında kullanılmıştır. Elde edilen alt fraksiyonların sitotoksik etkilerini açıklayabilmek amacıyla flow sitometri ile apoptotik ve BrdU kolorimetrik kit ile DNA sentez inhibisyonları üzerine etkileri araştırılmıştır. Ayrıca, olası antioksidan, antikolinesteraz ve anti-LOX aktiviteleri in vitro olarak belirlenmiştir. Bulgular değerlendirildiğinde, E2 kodlu alt fraksiyon pozitif kontrol olan mitoksantron ile kıyaslanabilir ölçüde A549 akciğer kanser hücre hatlarına karşı kayda değer sitotoksik etki göstermiştir. E3 ve E6 kodlu alt fraksiyonların meme ve akciğer kanser hücrelerine karşı iyi sitotoksik etki gösterdikleri belirlenmiştir. Bu üç alt fraksiyonun farklı konsantrasyonlarda DNA sentez inhibisyonu yaptıkları ve hücreleri apoptoza sürükledikleri görülmüştür. Diğer aktivite çalışmalarında kayda değer sonuçlar elde edilememiştir. Her alt fraksiyonun kimyasal bileşimi YBSK/KS-KS yöntemi ile araştırılmıştır. Hidroksisinnamik asit türevleri, lignan türevleri, fenolik aminler, oksilipinler gibi sekonder metabolitler alt fraksiyonlarda belirlenmiştir

Electrochemical Dimerization of Phenylpropenoids and the Surprising Antioxidant Activity of the Resultant Quinone Methide Dimers

A simple method for the dimerization of phenylpropenoid derivatives is reported. It leverages electrochemical oxidation of pâ unsaturated phenols to access the dimeric materials in a biomimetic fashion. The mild nature of the transformation provides excellent functional group tolerance, resulting in a unified approach for the synthesis of a range of natural products and related analogues with excellent regiocontrol. The operational simplicity of the method allows for greater efficiency in the synthesis of complex natural products. Interestingly, the quinone methide dimer intermediates are potent radicalâ trapping antioxidants; more so than the phenols from which they are derivedâ or transformed toâ despite the fact that they do not possess a labile Hâ atom for transfer to the peroxyl radicals that propagate autoxidation.Quinone methide dimers are prepared via mild anodic oxidation mediated by a cheap and readily available amine base with excellent yield and regiocontrol. This strategy provides rapid access to intermediates for the synthesis of phenylpropenoid oligomers in a catalytic fashion, providing a new tool for the total synthesis of these complex molecules.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147117/1/anie201810870-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147117/2/anie201810870_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147117/3/anie201810870.pd

Electrochemical Dimerization of Phenylpropenoids and the Surprising Antioxidant Activity of the Resultant Quinone Methide Dimers

A simple method for the dimerization of phenylpropenoid derivatives is reported. It leverages electrochemical oxidation of pâ unsaturated phenols to access the dimeric materials in a biomimetic fashion. The mild nature of the transformation provides excellent functional group tolerance, resulting in a unified approach for the synthesis of a range of natural products and related analogues with excellent regiocontrol. The operational simplicity of the method allows for greater efficiency in the synthesis of complex natural products. Interestingly, the quinone methide dimer intermediates are potent radicalâ trapping antioxidants; more so than the phenols from which they are derivedâ or transformed toâ despite the fact that they do not possess a labile Hâ atom for transfer to the peroxyl radicals that propagate autoxidation.Chinonmethidâ Dimere wurden durch milde anodische Oxidation vermittelt durch eine preiswerte und leicht verfügbare Aminbase mit exzellenter Ausbeute und Regiokontrolle hergestellt. Diese Strategie ermöglicht raschen Zugang zu Zwischenprodukten für die katalytische Synthese von Phenylpropenoidâ Oligomeren und bietet ein neues Werkzeug für die Totalsynthese dieser komplexen Moleküle.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146959/1/ange201810870.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146959/2/ange201810870_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146959/3/ange201810870-sup-0001-misc_information.pd

Antiplasmodial neolignans from Trema orientalis : identification, synthesis and analogue generation.

Includes abstract.Includes bibliographical references.Trema orientalis, a widely distributed evergreen tree with various medicinal properties including the treatment of malaria, was investigated as a potential source of new antimalarial lead compounds. Organic extracts of the young growing twigs of T. orientalis were reproducibly shown to be active against the chloroquine-sensitive (D10) and chloroquine resistant (K1) strains of Plasmodium falciparum. The 8-O-4' oxyneolignans, dadahols A and B, were identified as the major active compounds using two bioassay-guided fractionation approaches. The new accelerated “HPLC biogram” methodology allowed for early recognition of the active compounds in the complex plant extract, requiring considerably less time and material compared to the classical reiterative approach

Persistent Radicals in Natural Product Synthesis: A Biomimetic Approach to Resveratrol Oligomers

Since their discovery 120 years ago, carbon-centered free radicals have captivated the attention of organic chemists worldwide. As the thermodynamic and kinetic properties of radical reactions have been studied, it has been recognized that open-shell intermediates offer complementary and orthogonal modes of reactivity when compared to traditional polar mechanisms. Persistent radicals, which by definition have higher kinetic barriers for reactivity, serve to increase the selectivity with which radical reactions occur through the persistent radical effect – a phenomenon that has recently begun to be leveraged for synthesis. The work described herein seeks to advance the field of radical chemistry in the context of employing persistent radicals for synthesis through synergistic combination of physical organic chemistry and chemical synthesis. In particular, these efforts target chemical synthesis of oligomers from the resveratrol class of natural products – an extensive and structurally diverse set of polyphenols to which a broad range of biological activities has been ascribed – with the goal of better understanding the mechanism(s) by which these compounds are biologically active. Chapter 1 summarizes the state of the field of radical chemistry in the context of natural product synthesis, concluding with a discussion of how persistent radicals have begun to be employed. The inspiration for the synthetic approach described in the subsequent chapters derives from the final example in which, during the course of a natural product total synthesis campaign, a key equilibrium between persistent phenoxyl radicals and their dimeric adducts was discovered and leveraged to access C8–C8′ resveratrol dimers and tetramers. Chapter 2 details how a mild, sustainable, and scalable approach for the generation of these persistent radicals was developed by relying upon electrochemical oxidation. This new method enabled the synthesis of a set of natural product analogs for initial structure-activity relationship (SAR) analysis of the compounds as radical trapping antioxidants (RTAs). Surprisingly, it was determined during the course of this study that the persistent radicals are more potent RTAs than any of the polyphenols evaluated, calling into question the exact cellular role these compounds fulfill in nature. Finally, Chapter 3 describes how thermodynamic study of the equilibrium between the persistent phenoxyl radicals and the corresponding C8–C8′ dimers resulted in the discovery of a C8–C8′ to C3–C8′ homolytic bond migration. This reaction was subsequently leveraged as the key step for the synthesis of the resveratrol tetramers vitisin A and vitisin D – two members of a subset of resveratrol oligomers to which perhaps the most interesting biological activity has been attributed. This chapter concludes with a discussion of where this project is headed in terms of the use of these persistent radicals for intermolecular C8–C10′ bond-forming reactions to access resveratrol trimers. In total, the strategy developed herein for resveratrol oligomer synthesis mimics the proposed manner in which Nature constructs these complex molecules, offering a direct route for the evaluation of their pharmacological potential.PHDChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/155104/1/kevjrom_1.pd

Dihydrobenzofuran neolignans from Arum italicum

A mixture of two new enantiomeric dihydrobenzofuran neolignans has been isolated from Arum italicum. The structures have been determined on the basis of the physical data of the compounds. © 1994