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Taha Toros Arşivi, Dosya No: 24-Attila İlha

Recent insights about pyrrolidine core skeletons in pharmacology

To overcome numerous health disorders, heterocyclic structures of synthetic or natural origin are utilized, and notably, the emergence of various side effects of existing drugs used for treatment or the resistance of disease-causing microorganisms renders drugs ineffective. Therefore, the discovery of potential therapeutic agents that utilize different modes of action is of utmost significance to circumvent these constraints. Pyrrolidines, pyrrolidine-alkaloids, and pyrrolidine-based hybrid molecules are present in many natural products and pharmacologically important agents. Their key roles in pharmacotherapy make them a versatile scaffold for designing and developing novel biologically active compounds and drug candidates. This review aims to provide an overview of recent advancements (especially during 2015–2023) in the exploration of pyrrolidine derivatives, emphasizing their significance as fundamental components of the skeletal structure. In contrast to previous reviews that have predominantly focused on a singular biological activity associated with these molecules, this review consolidates findings from various investigations encompassing a wide range of important activities (antimicrobial, antiviral, anticancer, anti-inflammatory, anticonvulsant, cholinesterase inhibition, and carbonic anhydrase inhibition) exhibited by pyrrolidine derivatives. This study is also anticipated to serve as a valuable resource for drug research and development endeavors, offering significant insights and guidance

Yeni bir glioksim sentezi ve nikel(II), bakır(II), kobalt(II) ile komplekslerinin hazırlanması

TEZ1368Tez (Yüksek Lisans) -- Çukurova Üniversitesi, Adana, 1993.Kaynakça (s. 67-70) var.vii, 72 s. ; 30 cm.…Bu çalışma Ç.Ü. Bilimsel Araştırma Projeleri Birimi Tarafından Desteklenmiştir. Proje No: FBE.93.13

İzole kurbağa özofagus striplerinde nitrerjik mekanizma aracılığı ile oluşturulan gevşemeler üzerinde uvabain,sodyum metavanadat ve Amilorid'in etkileri

TEZ3466Tez (Doktora) -- Çukurova Üniversitesi, Adana, 2000.Kaynakça (s. 49-53) var.xi, 53 s. ; 30 cm.

EFFECTS OF SODİUM-POTASSİUM - EXCHANGİNG ATPASE AND NİTRİC OXİDE ON ETHANOL INDUCED RELAXATİONS

Alkol (etanol) dünyada yaygın olarak kullanılmakta olup gastrointestinal (GI) rahatsızlıklara neden olabilmektedir. Etanolün GI sistemde oluşturduğu etkilerin moleküler mekanizmasını aydınlatmak alkole bağlı GI sistem rahatsızlıklarının tedavi yaklaşımlarına katkı sağlayabilir. Bundan dolayı şimdiki çalışmada, GI sistem düz kas dokusu olan izole fare gastrik fundusunda etanolün oluş- turduğu etkilerin moleküler mekanizmasını araştırmayı amaçladık. Bu amaçla, ilgili dokuda etanol ile indüklenen gevşeme cevapları üzerinde nitrik oksid ve sodyum-potasyum değiştirici ATPaz'ın rolünü araştırdık. Gereç ve Yöntemler: Bu çalışmada her iki cinsten beyaz fare (Swiss albino) kullanıldı. Fareler servikal dislokasyon ile öldürüldükten sonra gastrik funduslar izole edildi. İzole edilen gastrik fundus dokuları longitudinal olarak kesilmek suretiyle gastrik fundus şeritleri hazırlandı ve içinde Tyrode solüsyonu bulunan organ banyosuna 0.5 g tansiyon altında asıldı. Banyo ortamı 37°C'de sabit tutuldu ve %95 O2 ve %5 CO2 ile gazlandırıldı. Deneysel veriler izometrik transduser vasıtasıyla kaydedildi. Bir saatlik dengelenme periyodundan sonra, izole fare gastrik fundus şeridinin bazal tonusu 5 dakika boyunca kaydedildi ve etanol organ banyosuna uygulandı (etanolun organ banyosu ortamındaki nihai konsantrasyonu 164 mM idi). Bulgular: Etanol (164 mM) izole fare mide fundus şeritlerinde tekrarlanabilir gevşemelere neden oldu. Bu gevşemeler NO sentaz enziminin potent ve spesifik inhibitörü olan N?-nitro-L-arginin (L-NOARG; 10-5 -5x10-4 M) tarafından konsantrasyona bağımlı bir şekilde inhibe edildi. Bu inhibisyon istatistiksel olarak anlamlı idi. Buna karşılık, sodyum-potasyum değiştirici ATPaz'ın potent ve spesifik inhibitörü olan uvabain (10-5 -10-4 M), izole fare gastrik fundus şeritlerinde etanol (164 mM) ile indüklenen gevşemeleri etkilemedi. Sonuç: Deneysel sonuçlar, izole fare gastrik fundus düz kasında etanol ile indüklenen gevşemelerde nitrik oksidin rolünün olabileceğini göstermektedir. Deneysel çalışma sonuçları aynı zamanda, ilgili dokuda etanol ile indüklenen gevşeme yanıtlarında sodyum-potasyum değiştirici ATPaz'ın rolünün olmadığını telkin etmektedir.Alcohol is widely used in the world and can cause gastrointestinal (GI) disturbances. Elucidating the molecular mechanism of alcohol in the GI tract may contribute to the therapeutic approaches on GI diseases caused by alcohol. So in the present study we aimed to elucidate the molecular mechanism of ethanol on isolated mouse gastric fundus. We investigated the role of nitric oxide and sodium-potassium-exchanging ATPase on relaxations induced by ethanol in the related tissue. Material and Methods: Mice (Swiss albino) of either sex were used in this study. After killing the mice by cervical dislocation the gastric fundal strips were prepared by longitudinal incision and mounted under 0.5 g tension in an organ bath filled with Tyrode’s solution. The bath medium was maintained at 37°C and gassed with 95% O2 and 5% CO2. After equlibrium period of an hour, the basal tonus of isolated mouse gastric fundal strip was recorded for 5 minutes and ethanol was applied into organ bath (the final concentration of ethanol in the organ bath medium was 164 mM). Results: Ethanol (164 mM) caused reproducible relaxations in isolated mouse gastric fundal strips. These relaxations were statistically significantly inhibited by N?-Nitro-L-arginine (L-NOARG; 10-5 -5x10-4 M), a potent and specific inhibitor of nitric oxide synthase, in a concentration dependent manner. On the other hand ouabain (10-5 -10-4M), a potent and specific inhibitor of the sodium-potassium-exchanging ATPase, failed to affect the relaxations induced by ethanol (164 mM) in the mouse gastric fundus. Conclusion: The results of experimental data suggest that nitric oxide may play a role on relaxations induced by ethanol in the isolated mouse gastric fundal smooth muscle. The results also suggest that sodium-potassiumexchanging ATPase may not have a role on relaxations induced by ethanol in the related tissue

Synthesis, crystal structure and antifungal/antibacterial activity of some novel highly functionalized benzoylaminocarbothioyl pyrrolidines

A series of novel highly functionalized benzoylaminocarbothioyl pyrrolidines were prepared from benzoylisothiocyanate and substituted pyrrolidines in excellent yield. The crystal structure of the novel 1- benzoylaminocarbothioyl-5-(naphthyl)-pyrrolidine-2,3,4-tricarboxylicacid trimethyl ester (3a) was determined by X-ray crystal structure analysis. The synthesized compounds were characterized and screened for their in vitro antibacterial and antifungal activities and toxicity. The prepared compounds were tested against the standard strains: Escherichia coli (ATCC 25922), Enterobacter cloacae (ATCC 13047), Enterococcus faecalis (ATCC 29212), Pseudomonas aeruginosa (ATCC 27853), Staphylococcus aureus (ATCC 29213) and Staphylococcus epidermidis (ATCC 12228) and the yeasts Candida albicans (ATCC 90028), Candida krusei (ATCC 6258), Candida parapsilosis (ATCC 22019), Candida tropicalis (ATCC 22019) and Candida glabrata (ATCC 32554)

Effects of sodium-potassium-exchanging ATPase and nitric oxide on ethanol induced relaxations [Etanol ile ındüklenen gevşemeler üzerinde sodyum-potasyum değiştirici ATPaz ve nitrik oksid’in etkileri]

Objective: Alcohol is widely used in the world and can cause gastrointestinal (GI) disturbances. Elucidating the molecular mechanism of alcohol in the GI tract may contribute to the therapeutic approaches on GI diseases caused by alcohol. So in the present study we aimed to elucidate the molecular mechanism of ethanol on isolated mouse gastric fundus. We investigated the role of nitric oxide and sodium-potassium-exchanging ATPase on relaxations induced by ethanol in the related tissue. Material and Methods: Mice (Swiss albino) of either sex were used in this study. After killing the mice by cervical dislocation the gastric fundal strips were prepared by longitudinal incision and mounted under 0.5 g tension in an organ bath filled with Tyrode’s solution. The bath medium was maintained at 37°C and gassed with 95% O2 and 5% CO2. After equlibrium period of an hour, the basal tonus of isolated mouse gastric fundal strip was recorded for 5 minutes and ethanol was applied into organ bath (the final concentration of ethanol in the organ bath medium was 164 mM). Results: Ethanol (164 mM) caused reproducible relaxations in isolated mouse gastric fundal strips. These relaxations were statistically significantly inhibited by N?-Nitro-L-arginine (L-NOARG; 10-5-5×10-4 M), a potent and specific inhibitor of nitric oxide synthase, in a concentration dependent manner. On the other hand ouabain (10-5-10-4 M), a potent and specific inhibitor of the sodium-potassium-exchanging ATPase, failed to affect the relaxations induced by ethanol (164 mM) in the mouse gastric fundus. Conclusion: The results of experimental data suggest that nitric oxide may play a role on relaxations induced by ethanol in the isolated mouse gastric fundal smooth muscle. The results also suggest that sodium-potassiumexchanging ATPase may not have a role on relaxations induced by ethanol in the related tissue. © 2017 by Türkiye Klinikleri

Characterization of nicotinic cholinergic receptors

Objective: To characterize nicotinic cholinergic receptors (cholinoceptors) in frog rectus abdominis and mouse esophagus. Material and Methods: Isolated preparations of mouse esophagus and frog rectus abdominis were separately mounted in organ baths filled with Krebs and Ringer solutions respectively. The organ bath medium was continuously gassed with 95% O2 and 5% CO2 and the temperature was maintained at 37°C and 25°C for mouse esophagus and frog rectus abdominis respectively. Changes in muscle length were recorded by isotonic transducers. The effects of neuromuscular blocking agents were investigated on contractions mediated by nicotinic cholinoceptors in both the preparations. Results: The contractions induced by carbachol (Cch) (5×10-6-5×10-5 M) were significantly inhibited by pancuronium (10-9-5×10-8) in mouse esophagus and frog rectus abdominis. Gallamine inhibited the contractions in the frog rectus abdominis but it failed to reduce the Cch responses in the mouse esophagus. On the other hand, d-tubocurarine caused irreversible contractions in the basal tonus of frog rectus abdominis, but it reduced the contractions evoked by Cch in mouse esophagus. Conclusion: The different effects of the neuromuscular blocking agents on contractions mediated by nicotinic cholinoceptors in frog rectus abdominis and mouse esophagus indicated that the nicotinic cholinoceptors in two different tissues may not be identical and these differences may be attributed to the different nicotinic cholinoceptor subtypes

The influence of nitric oxide donors on the responses to nitrergic nerve stimulation in the mouse duodenum

PubMedID: 11399268We investigated whether exogenous nitric oxide (NO) donors have a prejunctional and/or postjunctional inhibitory effect on the nitrergic responses and whether this inhibitory effect was mediated by NO itself and in part, by cyclic GMP in mouse duodenal strips. N?-nitro-L-arginine inhibited relaxations induced by electrical field stimulation of nitrergic nerves, but not those with acidified NaNO2. Furthermore, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) inhibited both types of relaxations while 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT) and N-ethylmaleimide were ineffective. NO donors, nitroglycerin and sodium nitroprusside, inhibited relaxations induced by nitrergic nerve stimulation, but not those with acidified NaNO2. Hemoglobin, exogenous Cu2+/Zn2+ superoxide dismutase, diethyldithiocarbamic acid and pyrogallol did not influence the relaxation with nitrergic nerve stimulation. However, hemoglobin, diethyldithiocarbamic acid, pyrogallol and diethyldithiocarbamic acid plus pyrogallol attenuated the inhibitory effect of NO donors on relaxation with nitrergic nerve stimulation, and exogenous superoxide dismutase potentiated this inhibitory effect. Moreover, nitrergic nerve-mediated relaxations were inhibited by 8-bromo-cyclic GMP, but not by 8-bromo-cyclic AMP. These results suggest that exogenous NO donors have a prejunctional inhibitory effect on the nerve-mediated nitrergic relaxation and that the inhibitory effects of nitroglycerin and sodium nitroprusside are NO-dependent, but not related to NO metabolites such as peroxynitrite or a nitrosothiol intermediate. However, a contribution of S-nitrosothiol formed intracellularly cannot be entirely ruled out. Also, this prejunctional inhibition is mediated, at least in part, by the cyclic GMP, but not the cyclic AMP, pathway. © 2001 Elsevier Science B.V.TF.99.6We are indebted to Dr. S. Cellek (The Wolfson Institue for Biomedical Research, University College London) for the gift of 1 H -[1,2,4]oxadiazolo[4,3- a ]quinoxalin-1-one. We thank Mr. Kenan Daglıoglu (Çukurova University Experimental Research Center) for the supply of mice. This work was supported by Çukurova University Research Foundation (TF.99.6) and parts of this work were presented at the annual meeting of the European Pharmacological Societies, Budapest, Hungary, 3–7 July 1999

Contribution of phospholipase C and protein kinase C but not endothelin-converting enzyme to contractile responses of ethanol [Etanolüün kontraktil cevaplarında endotelin dönüştürücü enzimin degil, fosfolipaz C ve proteinkinaz C'nin katkısı]

Aim: To evaluate the possible roles of phospholipase C, protein kinase C, and endothelin-converting enzyme on contractions induced by ethanol (164 mM) in isolated gastric fundal strips of mice. Materials and methods: After the mice were killed, the stomach of each was removed and longitudinal muscle strips were prepared from the gastric fundus. The strips were mounted in organ baths and their responses were recorded isometrically. Ethanol (164 mM) was added to the organ baths and a steady-state contraction was obtained. After the first ethanol response was recorded, the preparations were incubated separately with lidocaine (1-100 µM), neomycin (10-500µµM), safingol (0.5-5µµM), and SM-19712 (1-50 µM) for 40 min. The second ethanol response was then examined in the presence of the drug used in the incubation period. Results: Lidocaine (1-100 µM), a local anesthetic agent, did not modulate the contractions induced by ethanol in isolated gastric fundal strips of mice. In contrast, neomycin (10-500 µM), a selective inhibitor of phospholipase C, and safingol (0.5-5 µM), a selective inhibitor of protein kinase C, decreased the ethanol-induced contractions. SM-19712 (1-50 µM), a selective inhibitor of endothelin-converting enzyme, failed to affect these contractions. Conclusion: The contractile effect of ethanol may be muscular rather than neuronal in the gastric fundal strips of mice. In addition, phospholipase C and protein kinase C pathways may have a role in contractions due to ethanol in the mouse gastric fundus. On the other hand, endothelin-converting enzyme may not have a regulatory role in the contractile responses of ethanol in the same tissue. © TÜBİTAK