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TOPÇU, GÜLAÇTI

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GÜLAÇTI
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Start date: 2020 × End date: 2023 × Has files: true ×

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Now showing 1 - 9 of 9
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    PublicationOpen Access
    Triterpenoids and steroids isolated from Anatolian Capparis ovata and their activity on the expression of inflammatory cytokines
    (2020-01-01T00:00:00Z) GAZİOĞLU, IŞIL; Semen, Sevcan; Acar, Ozden Ozgun; KOLAK, Ufuk; Sen, Alaattin; TOPÇU, GÜLAÇTI; GAZİOĞLU, IŞIL; TOPÇU, GÜLAÇTI
    Context: Capparis L. (Capparaceae) is grown worldwide. Caper has been used in traditional medicine to treat various diseases including rheumatism, kidney, liver, stomach, as well as headache and toothache. Objective: To isolate and elucidate of the secondary metabolites of the C. ovata extracts which are responsible for their anti-inflammatory activities. Materials and methods: Buds, fruits, flowers, leaves and stems of C. ovata Desf. was dried, cut to pieces, then ground separately. From their dichloromethane/hexane (1:1) extracts, eight compounds were isolated and their structures were elucidated by NMR, mass spectroscopic techniques. The effects of compounds on the expression of inflammatory cytokines in SH-SY5Y cell lines were examined by qRT-PCR ranging from 4 to 96 mM. Cell viability was expressed as a percentage of the control, untreated cells. Results: This is a first report on isolation of triterpenoids and steroids from C. ovata with anti-inflammatory activity. One new triterpenoid ester olean-12-en-3b,28-diol, 3b-pentacosanoate (1) and two new natural steroids 5a,6a-epoxycholestan-3b-ol (5) and 5b,6b-epoxycholestan-3b-ol (6) were elucidated besides known compounds; oleanolic acid (2), ursolic acid (3), b-sitosterol (4), stigmast-5,22-dien-3b-myristate (7) and bismethyl-octylphthalate (8). mRNA expression levels as EC10 of all the tested seven genes were decreased, particularly CXCL9 (19.36-fold), CXCL10 (8.14-fold), and TNF (18.69) by the treatment of 26 mM of compound 1 on SH-SY5Y cells. Discussion and conclusions: Triterpenoids and steroids isolated from C. ovata were found to be moderate-strong anti-inflammatory compounds. Particularly, compounds 1 and 3 were found to be promising therapeutic agents in the treatment of inflammatory and autoimmune diseases.
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    PublicationOpen Access
    Special issue dedicated to the memory of Professor Ayhan Ulubelen (1931-2020)
    (2021-01-01T00:00:00Z) TOPÇU, GÜLAÇTI; TOPÇU, GÜLAÇTI
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    PublicationOpen Access
    Bioguided Isolation of Secondary Metabolites from Salvia cerino-pruinosa Rech. f. var. cerino-pruinosa
    (2021-11-01T00:00:00Z) Ertas, Abdulselam; Cakirca, Hatice; Yener, Ismail; Akdeniz, Mehmet; Fırat, Mehmet; TOPÇU, GÜLAÇTI; KOLAK, Ufuk; TOPÇU, GÜLAÇTI
    In the current study, the ethanol extracts prepared from the aerial parts and roots of an endemic species, Salvia cerino-pruinosa Rech. f. var. cerino-pruinosa were fractionated on silica gel columns and tested for determination of their antioxidant activity using DPPH free radical and ABTS cation radical scavenging, and cupric reducing antioxidant capacity (CUPRAC) test assays. Twenty known secondary metabolites were isolated from the active antioxidant fractions; rosmarinic acid (1), chlorogenic acid (2), caffeic acid (3), 4-hydroxybenzoic acid (4), benzoic acid (5), luteolin 7-O-glucoside (6), bis-(2-ethylhexyl)benzene-1,2-dicarboxylate (7), salvianolic acid A (8), salvianolic acid B (9), 7-acetylroyleanone (10), 6,7-dehydroroyleanone (11), ferruginol (12), inuroyleanol (13), 12-hydroxy-6,7-secoabieta-8,11,13-triene-6,7-dial (14), ursolic acid (15), oleanolic acid (16), taraxasterol (17), lupenone (18), beta-sitosterol (19), and stigmasterol (20). Rosmarinic acid, which was obtained from the aerial parts, was found to be the best antioxidant compound among the isolated secondary metabolites in DPPH free radical and ABTS cation radical scavenging, and CUPRAC assays (IC50: 1.20 +/- 0.04 mu g/mL, IC50: 1.74 +/- 0.06 mu g/mL, A(0.5): 1.22 +/- 0.02 mu g/mL, respectively). Chlorogenic and caffeic acids, luteolin 7-O-glucoside, salvianolic acids A and B, and inuroyleanol exhibited also high antioxidant activity in the mentioned assays.
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    PublicationOpen Access
    Isoquinoline alkaloids isolated from Glaucium corniculatum var. corniculatum and Glaucium grandiflorum subsp. refractum var. torquatum with bioactivity studies
    (2023-06-01) Kuşman Sayğı T.; Tan N.; Alim Toraman G. Ö.; Gürer Ç.; Tugay O.; Topçu G.; ALİM TORAMAN, GÜLBAHAR ÖZGE; TOPÇU, GÜLAÇTI
    Context: The genus Glaucium Mill., one of the important Papaveraceae family plants, is rich in isoquinoline alkaloids and distributed worldwide. Objective: Isolation and identification of bioactive alkaloids from Glaucium grandiflorum Boiss. & Huet. subsp. refractum (Nabelek) Mory var. torquatum (Cullen) Mory and G. corniculatum (L.) Rudolph var. corniculatum (Aslan 2012), and investigation of their antioxidant and anticholinesterase activities. Materials and methods: The aerial parts of each plant were dried, powdered, and percolated with methanol, then each extract was fractionated between 50% aqueous acetic acid and petroleum. Their aqueous acidic layer was adjusted to pH 7-8 with NH4OH and extracted with chloroform, the extract was subjected to CC separation and isolation. Structures of the isolated alkaloids were elucidated by 1D and 2D-NMR and mass spectral analyses. The alkaloid extracts and their pure alkaloids were tested for anti-cholinesterase (AChE and BuChE) and antioxidant (ABTS, CUPRAC, β-carotene linoleic acid tests) activities in vitro. Results: Methanol extracts of Glaucium grandiflorum subsp. refractum var. torquatum and G. corniculatum var. corniculatum afforded a novel compound glauciumoline and seven known isoquinoline alkaloids three of which have an aporphine-type and the other five have a protopine-type skeleton. Among them, trans-protopinium (7) and cis-protopinium (8) were isolated from a Glaucium species for the first time. Tertiary amine extracts (TAEs) of both plants showed very strong acetylcholinesterase inhibitory activity. The TAE of the plants also showed strong antioxidant activity while the isolated alkaloids showed no meaningful activity in the anticholinesterase and antioxidant tests. Discussion and conclusions: Glaucium species are considered promising therapeutic agents in the treatment of Alzheimer's disease.
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    PublicationOpen Access
    Anti-SARS-CoV-2 and cytotoxic activity of two marine alkaloids from green alga Caulerpa cylindracea Sonder in the Dardanelles
    (2022-10-01T00:00:00Z) Erol, Ebru; Alim Toraman, Gulbahar Ozge; Orhan, Muge Didem; Avsar, Timucin; Akdemir, Atilla; Okudan, Emine Sukran; Topcu, Gulacti; EROL, EBRU; AKDEMİR, ATİLLA; ALİM TORAMAN, GÜLBAHAR ÖZGE; TOPÇU, GÜLAÇTI
    Caulerpa cylindracea Sonder is a green alga belonging to the CauIerpaceae family. This is the first chemical investigation of C. cylindracea in the Dardanelles which resulted in the isolation of four compounds, caulerpin (1), monomethyl caulerpinate (2), beta-sitosterol (3), and palmitic acid (4). Their structures were elucidated by spectroscopic analyses including 1D- and 2D NMR and mass. The isolated compounds 1 and 2 were tested against the SARS-CoV-2 viral targets spike protein and main protease (3CL) enzyme, and both compounds significantly inhibit the interaction of spike protein and ACE2, while the main protease activity was not significantly reduced. Docking studies suggested that compounds 1 and 2 may bind to the ACE2 binding pocket on spike, and compound 2 may aka bind to an allosteric site on spike. As such, these compounds may inhibit the spike-ACE2 complex formation competitively and/or allosterically and have the potential to be used against SARS-CoV-2 virus infection. In addition, compounds 1 and 2 showed at [east two-fold higher cytotoxicity against breast cancer cell Lines MCF7 and MDA-MB-231 compared to the CCD fibroblast control cell Line
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    PublicationOpen Access
    Selective in-vitro Enzymes- Inhibitory Activities of Fingerprints Compounds of Salvia Species and Molecular Docking Simulations
    (2020-01-01T00:00:00Z) ÖZHAN KOCAKAYA, ŞAFAK; ERTAŞ, ABDULSELAM; Yener, Ismail; Ercan, Bahadir; VARHAN ORAL, ELİF; Akdeniz, Mehmet; Kaplaner, Erhan; TOPÇU, GÜLAÇTI; Kolak, Ufuk; TOPÇU, GÜLAÇTI
    Recently Nutrition and Food Chemistry researches have been focused on plants and their products or their secondary metabolites having anti-alzheimer, anti-cancer, anti-aging, and antioxidant properties. Among these plants Salvia L. (Lamiaceae) species come into prominence with their booster effects due to high antioxidant contents, which have over 900 species in the world and 98 in Turkey. Some Salvia species are already in use as herbal treatment of vessel stiffness, Dementia like problems and cancer. Recently some species of Salvia are of extensive research topic. In this study, inhibitory potentials of secondary metabolites, rosmarinic acid, salvigenin, salvianolic acid A and B, tanshinone I and IIA, cyrtotanshinone, dihydrotanshinone I, carnosic acid, carnosol, and danshensu sodium salt were investigated against acetylcholinesterase, butyrylcholinesterase, urease and tyrosinase enzymes both in-vitro and in slico in detail. Elevated inhibitory effects on acetyl-and butyryl-cholinesterase of dihydrotanshinone I (IC50: 1.50 +/- 0.02 and 0.50 +/- 0.01 mu g/mL, respectively), carnasol (IC50: 11.15 +/- 0.05 ve 3.92 +/- 0.03 mu g/mL) and carnosic acid (IC50: 31.83 +/- 0.65 ve 4.12 +/- 0.04 mu g/mL) were observed. Furthermore, all other secondary metabolites were active against butyrylcholinesterase. Anti-urease (42.41 +/- 0.85%) and anti-tyrosinase (39.82 +/- 1.16%) activities of tanshinone I were also observed. Potential inhibitory effects of these molecules on target proteins were investigated using DOCK and molecular dynamics calculations. Dock score analysis and Lipinski parameters were demonstrated that these ligands are potential inhibitors against relevant enzymes. Our findings suggest that Salvia species can be utilized as a ptential source of anti-alzheimer active compounds for designing novel products.
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    PublicationOpen Access
    Natural Alkaloids as Potential Anti-Coronavirus Compounds
    (2020-12-01T00:00:00Z) Topçu, Gülaçtı; Şenol, Halil; Alim Toraman, Gülbahar Özge; Altan, Vecdi Melih; TOPÇU, GÜLAÇTI; ŞENOL, HALIL; ALİM TORAMAN, GÜLBAHAR ÖZGE; ALTAN, VECDİ MELİH
    Coronaviruses are causative agents of the last three epidemics/pandemic; Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) and the last one Severe Acute Respiratory Syndrome-Cov-2 (SARS-CoV-2). Although meta-analysis of treatment studies against these three coronaviruses found no clear benefit of any spesific regimen, currently, remdesivir and favipiravir are promising potential therapies for SARS-CoV-2. On the other hand, since natural products have always played a crucial role in drug discovery and development process against various diseases, many groups in the world, are now trying to find new or repurposed natural or naturally originated drugs against viruses and coronaviruses. Secondary metabolites of the plants, particularly alkaloids and terpenoids have been exhibited strong antimicrobial and anticancer activities besides synthetic drugs and other natural compounds (nucleosides and nucleotides and bacterial and fungi originated ones). The first isolated secondary metabolites have been converted into important drugs since 1800’s such as morphine, codeine, cocaine, and quinine have alkaloid skeleton as well as some of the recent anticancer drugs vinblastine, vincristine, taxol, etc. This review includes the last two decades of publications about natural alkaloids rather than their plant extracts which showed some promising results against coronaviruses. Marine organisms are also another rich source to discover new lead drugs, however they were excluded in the present review article.
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    PublicationOpen Access
    Synthesis and anticancer activity of novel derivatives of α,β‐unsaturated ketones based on oleanolic acid: in vitro and in silico studies against prostate cancer cells
    (2023-08-01) Şenol H.; Ghaffari-Moghaddam M.; Bulut Ş.; Akbaş F.; Köse A.; Topçu G.; ŞENOL, HALIL; AKBAŞ, FAHRİ; TOPÇU, GÜLAÇTI
    Herein, new derivatives of α,β-unsaturated ketones based on oleanolic acid (4 a-i) were designed, synthesized, characterized, and tested against human prostate cancer (PC3). According to the in vitro cytotoxic study, title compounds (4 a-i) showed significantly lower toxicity toward healthy cells (HUVEC) in comparison with the reference drug doxorubicin. The compounds with the lowest IC50 values on PC3 cell lines were 4 b (7.785 μM), 4 c (8.869 μM), and 4 e (8.765 μM). The results of the ADME calculations showed that the drug-likeness parameters were within the defined ranges according to Lipinski's and Jorgensen's rules. For the most potent compounds 4 b, 4 c, and 4 e, a molecular docking analysis using the induced fit docking (IFD) protocol was performed against three protein targets (PARP, PI3K, and mTOR). Based on the IFD scores, compound 4 b had the highest calculated affinity for PARP1, while compound 4 c had higher affinities for mTOR and PI3K. The MM-GBSA calculations showed that the most potent compounds had high binding affinities and formed stable complexes with the protein targets. Finally, a 50 ns molecular dynamics simulation was performed to study the behavior of protein target complexes under in silico physiological conditions.
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    PublicationOpen Access
    Emodin and aloe-emodin, two potential molecules in regulating cell migration of skin cells through the MAP kinase pathway and affecting Caenorhabditis elegans thermotolerance
    (2023-12-01) GÜNAYDIN AKYILDIZ, AYŞENUR; Yanikoglu R. S.; Gulec M.; ALİM TORAMAN, GÜLBAHAR ÖZGE; Kuran E. D.; Atasoy S.; Olgun A.; Topcu G.; TOPÇU, GÜLAÇTI; ATASOY, SEZEN; GÜNAYDIN AKYILDIZ, AYŞENUR; ALİM TORAMAN, GÜLBAHAR ÖZGE; YANIKOĞLU, RABİA SARE
    Background: Emodin and aloe-emodin are two anthraquinones having positive effects in wound healing. However, their mechanism of action of wound healing is not fully understood. The MAP kinase family, which plays an active role in wound healing, is a well-characterized large family of serine/threonine kinases and regulates processes such as proliferation, oncogenesis, differentiation, and inflammation in the cell. The aim of this study is to comparatively elucidate the mechanisms of action of emodin and aloe-emodin, which are potential agents in wound healing. Methods: The mechanism of the effects of emodin and aloe-emodin on cell viability and cell migration was examined using the human skin fibroblast (CCD-1079Sk) cell line. The gene expression levels of the MAP kinases (JNK, P38, ERK) in the skin fibroblast cells along with a molecular docking study analyzing their interaction potential were evaluated. Furthermore, the molecules’ effects on the lifespan of Caenorhabditis elegans were studied. Results: Emodin and aloe-emodin inhibited the ATP content of the cells in a concentration dependent manner and accelerated cell migration at the lower concentrations while inhibiting cell migration in the higher concentration treatment groups. The expressions of JNK and P38 were upregulated at the low concentrations and downregulated at the higher concentrations. The molecular docking studies of the molecules gave high docking scores indicating their interaction potential with JNK and P38. C. elegans lifespan under heat stress was observed longer after 75 µM emodin and was significantly reduced after 150 µM aloe-emodin treatment. Conclusion: Aloe-emodin was found to be more potent on cell viability, cell migration, gene expression levels of the MAP kinases in healthy fibroblastic skin cells, and on the lifespan of C. elegans. This study reveals the functional effects and the biological factors that interact in the wound healing process of emodin and aloe-emodin, and give a possible treatment alternative to shorten the duration of wound care.