Bilge Sener

Inhibitory Activity of Marine Sponge-Derived Natural Products against Parasitic Protozoa

In this study, thirteen sponge-derived terpenoids, including five linear furanoterpenes: furospinulosin-1 (1), furospinulosin-2 (2), furospongin-1 (3), furospongin-4 (4), and demethylfurospongin-4 (5); four linear meroterpenes: 2-(hexaprenylmethyl)-2-methylchromenol (6), 4-hydroxy-3-octaprenylbenzoic acid (7), 4-hydroxy-3-tetraprenyl-phenylacetic acid (8), and heptaprenyl-p-quinol (9); a linear triterpene, squalene (10); two spongian-type diterpenes dorisenone D (11) and 11β-acetoxyspongi-12-en-16-one (12); a scalarane-type sesterterpene; 12-epi-deoxoscalarin (13), as well as an indole alkaloid, tryptophol (14) were screened for their in vitro activity against four parasitic protozoa; Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani and Plasmodium falciparum. Cytotoxic potential of the compounds on mammalian cells was also assessed. All compounds were active against T. brucei rhodesiense, with compound 8 being the most potent (IC50 0.60 μg/mL), whereas 9 and 12 were the most active compounds against T. cruzi, with IC50 values around 4 μg/mL. Compound 12 showed the strongest leishmanicidal activity (IC50 0.75 μg/mL), which was comparable to that of miltefosine (IC50 0.20 μg/mL). The best antiplasmodial effect was exerted by compound 11 (IC50 0.43 μg/mL), followed by compounds 7, 10, and 12 with IC50 values around 1 μg/mL. Compounds 9, 11 and 12 exhibited, besides their antiprotozoal activity, also some cytotoxicity, whereas all other compounds had low or no cytotoxicity towards the mammalian cell line. This is the first report of antiprotozoal activity of marine metabolites 1–14, and points out the potential of marine sponges in discovery of new antiprotozoal lead compounds.

Hypoglycaemic effect of Momordica charantia extracts in normoglycaemic or cyproheptadine-induced hyperglycaemic mice

The hypoglycaemic effect of orally administered extracts of Momordica charantia L. fruits was examined in normoglycaemic or cyproheptadine-induced hyperglycaemic mice. The aqueous extract reduced the fasting glucose levels of hyperglycaemic or normoglycaemic mice. However, the ethanol extract did not affect the fasting or nonfasting glucose levels significantly in both groups of mice. There was no significant difference between the glucose-loaded and glucose-loaded plus aqueous extract given group. On the other hand, oral glucose-loading of the cyproheptadine-induced hyperglycaemic animals reduced the fasting glucose levels significantly. These results showed that aqueous extract of M. charantia fruits has a hypoglycaemic activity without improving the tolerance to glucose in cyproheptadine-induced diabetic mice.

Activity of Turkish medicinal plants against mosquitoes Aedes aegypti and Anopheles gambiae

Organosoluble extracts from 55 Turkish medicinal plants were tested under standardised conditions for biological activity against third-instar larvae of mosquitoes Aedes aegypti and Anopheles gambiae. Eight extracts demonstrated significant larvicidal activity, with An. gambiae being more susceptible than Ae. aegypti in all cases. The possibility of using indigenous plants for mosquito control is discussed.RésuméDes extraits organosolubles provenant de 55 plantes médecinales de Turquie ont été testés sous conditions standardisées pour leur activité biologique sur des larves du 3è stade d’Aedes aegypti et Anopheles gambiae. Huit extraits ont démontré une activité larvicide significative, avec An. gambiae étant plus susceptible qu’Ae. aegypti dans tous les cas. Les possibilités d’utilisation des plants indigènes pour la lutte contre moustiques a été discutée.

Contemporary Anticholinesterase Pharmaceuticals of Natural Origin and Their Synthetic Analogues for the Treatment of Alzheimers Disease

Alzheimers disease (AD), the most common form of dementia, is a degenerative and progressive neurological disorder characterized by deficit in the cholinergic transmission and formation of senile plaques containing beta-amyloid protein in the brain. Although complete pathology of the disease has not been fully elucidated yet, there are several treatment strategies for AD treatment. The complexity of AD is also due to involvement of several enzymes through its progression. Therefore, the most important therapeutic approach has emerged as inhibition of acetylcholinesterase (AChE), which is the key enzyme in the breakdown of acetylcholine. Another very attractive approach to lower beta-amyloid protein in fibrillar form has been the alpha- and beta-secretase inhibitors. On the other hand, recently, N-methyl-D-aspartate (NMDA) receptor antagonists have become a strong alternative, which has been approved to be effective in treatment of moderate to severe type of AD. Within the past few years, some pharmaceuticals have become available for clinical use; however, none of them have been shown to possess ability to discontinue the disease up to date. Hence, there is obviously a great need for discovery of new drug candidates of natural or synthetic origins for AD treatment. This review will cover AChE-inhibiting pharmaceuticals from plants and their synthetic derivatives including relevant patent literatures which may promise a future hope for AD treatment.

Acetylcholinesterase, butyrylcholinesterase, and tyrosinase inhibition studies and antioxidant activities of 33 Scutellaria L. taxa from Turkey

The members of Scutellaria L. (Lamiaceae) is known to be rich particularly in flavonoids and among them, S. baicalensis has been recorded to be used for memory-enhancing purpose. Therefore, we initiated a study to screen the methanol extracts prepared from the aerial parts of 33 Turkish Scutellaria species for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities, which are the key enzymes taking place in pathogenesis of Alzheimers disease. Besides, the methanol extracts were tested in vitro against another enzyme, tyrosinase, which is associated with melanin hyperpigmentation. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenger effect, ferrous ion-chelating ability, and ferric-reducing antioxidant power (FRAP) of the ethyl acetate and methanol extracts were also determined. AChE, BChE, and tyrosinase inhibition of the extracts were performed on ELISA microplate reader by spectrophotometric method. The extracts showed weak inhibition against AChE and BChE, while the best tyrosinase inhibition was caused by the methanol extract of S. brevibracteata subsp. subvelutina. The extracts had a very high DDPH radical scavenging effect and moderate antioxidant activity in ferrous ion-chelating and FRAP tests.

Polyprenyl-hydroquinones and -furans from three marine sponges inhibit the cell cycle regulating phosphatase CDC25A.

The CDC25 phosphatases regulate the cell division cycle by controlling the activity of cyclin-dependent kinases. While screening for inhibitors of phosphatases among natural products we repeatedly found that some polyprenyl-hydroquinones and polyprenyl-furans (furanoterpenoids) (furospongins, furospinosulins) were potent CDC25 phosphatase inhibitors. These compounds were extracted, isolated and identified independently from three sponge species (Spongia officinalis, Ircinia spinulosa, Ircinia muscarum), collected at different locations in the Mediterranean Sea. The compounds were inactive on the Ser/Thr phosphatase PP2C-α and on three kinases (CDK1, CDK5, GSK-3), suggesting that some potent and selective CDC25 phosphatase might be designed from these initial structures.

Antiviral activities in extracts of Turkish medicinal plants

A total of 16 ethanol extracts of Turkish medicinal plants were evaluated for antiviral activities against herpes simplex virus (HSV) and Sindbis virus (SINV). Extracts of Galanthus elwesii and Rheum ribes showed the most potent anti-HSV activities, while six other extracts had weaker activities. Galanthus elwesii and Leucojum aestivum were the most potent anti-SINV extracts with four others showing weaker activities. In total, five extracts were active against both viruses, three were selective for HSV and one was selective for SINV. Evidence for an antiviral photosensitizer was obtained in two anti-HSV extracts, in which activity was either completely dependent on light, or was con-siderably enhanced by light. Thus, several Turkish medicinal plants appear to be promising sources of antiviral activities.

Antioxidant and anticholinesterase assets and liquid chromatography-mass spectrometry preface of various fresh-water and marine macroalgae.

The ethanol extracts from the fresh-water algae; Chara hispida L., Cladophora glomerata (Dilw.) Kόtz, C. fracta (Dilw.) Kόtz, Spirogyra gratiana Transeau, Mougeotia sp. (C.A. Agardh), Vaucheria sessilis (Vauch.) De Candolle, Geminella mutabilis (Breb.) Wille, the fresh-water plants; Ranunculus rionii Lagger and Ceratophyllum demersum L., as well as the marine algae; Sciniaia furcellata (Turn.) J. Agardh, Dictyota dichotoma (Huds.) Lam., Padina vickersiae Hoyt, Halopteris scoparia (L.) Sauvagau, and the sea grass; Posidonia oceanica (L.) Dell. were assessed in vitro for their antioxidant and anti-acetylcholinesterase (AChE) activities. Antioxidant activity was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity test at 0.125, 0.25, 0.5, 1.0, and 2.0 mg ml -1 and ferric-reducing antioxidant power assay (FRAP) at 0.5, 1.0, and 2.0 mg ml −1 concentrations. Total phenolic contents of the extracts were determined using Folin-Ciocalteaus reagent. The extracts were further analyzed qualitatively by LC-DAD-MS. S. gratiana had the best antioxidant activity, followed by R. rionii. LC-DAD-MS showed rich gallic acid and its ethyl ester contents in S. gratiana , while prosperous vitamin C content has been detected in P. oceanica for the first time in this study. S. gratiana possessed the highest inhibition (42.5±2.28%) at 2.0 mg ml −1 against AChE.

Free Radical Scavenging Activities of Some Edible Fruit Seeds

Free radical scavenging activity of the seeds of some edible fruits from Turkey, namely Citrus limon (L.) Burm. (lemon), Prunus armeniaca L. (wild apricot), P. laurocerasus L. (cherry laurel), P. cerasus L. (sour cherry), Citrullus vulgaris Schrader (watermelon), and Cucumis melo L. (melon), has been investigated by using stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH.) and superoxide (O 2 -) generated by xanthine/xanthine oxidase (XOD) systems. DPPH. scavenger capacity of the extracts of the aforementioned edible fruit seeds was compared with the known antioxidative substances such as tert -butyl-4-hydroxytoluene (BHT), vitamin C, quercetin and gallic acid. Radical scavenging capacity of the extracts was compared with that of gallic acid.

Biological activities of some Turkish medicinal plants

Turkey has an extraordinarily rich flora and wide knowledge of their indigenous medicinal plants. Medicinal plants constitute an important componbnt of flora and are widely distributed in different floristic regions of Turkey. Historically, plants have supplied the chemistry for over 25 % of prescription drugs used in human medicine( 1) and such biologically active plants have also provided leads to natural insecticides(2). Accordingly, we are investigating the potential of Turkish medicinal plants as a resource of new chemistry for public health and plant protection. The biological evaluation of substances from plant sources is highly releavant for the identification of lead compounds which can result in the development of novel and safe medicinal agents. During our extensive studies with Turkish medicinal plants, we have isolated and characterized a large number of natural products. On the other hand, a more systematical approach to the discovery of drugs from these plants has been initiated using bioassay-guided fractionation. At the end of this fractionation of selected plant extracts has resulted in the identification of active compounds representing a wide range of structures, including alkaloids, terpenoids and phenolic compounds(3). Fifty five organosoluble extracts prepared from Turkish medicinal plants were investigated for their biological activities against insects, nematodes, plant pathogens and brine shrimp in addition to their biological activities such as antimalarial, anticholinergic, analgesic and antiplatelet activities.