Browsing by Author "Taslimi, Parham"

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Co and Zn Metal Phthalocyanines With Bulky Substituents: Anticancer, Antibacterial Activities and Their Inhibitory Effects on Some Metabolic Enzymes With Molecular Docking Studies
(Taylor & Francis Ltd, 2022) Turkan, Fikret; Taslimi, Parham; Cabir, Beyza; Agirtas, Mehmet Salih; Erden, Yavuz; Celebioglu, Hasan Ufuk; Gulcin, Ilhami
In this study, we reported the synthesis of new cobalt and zinc phthalocyanine compounds with ((ethylenediamine-N,N',N'-triacetic acid-N-2-ethyl)oxy) (ETAEO) substituted groups. Characterization studies and anticancer properties of both synthesized compounds were determined as well. The inhibitory effects of these complexes on some metabolic enzymes were examined and it was observed that the enzymes inhibited by complex molecules at the micromolar levels. In addition, the active sites of the enzymes were determined by molecular modeling programme for screening the enzyme-inhibitor interactions. The molecular docking method was used to calculate the interactions of molecules with enzymes. Also, human prostate and breast cancer cell lines (PC-3 and MCF-7) were used to determine the anticancer properties of the complexes. All doses of the tetrakis (ETAEO) phthalocyaninato Cobalt II (1) did not show any significant changes in PC-3 cell viability, but significantly reduced in MCF-7 cell viability. Similarly, all doses of the tetrakis (ETAEO) phthalocyaninato zinc II (2) significantly reduced MCF-7 cell viability compared to the control and solvent control groups. According to the enzyme inhibition studies, both complexes showed the best inhibition effects for alpha-Glycosidase enzyme with 125.85 +/- 30.35 mu M and 165.30 +/- 27.18 mu M Ki values.
Determination of Anticancer Properties and Inhibitory Effects of Some Metabolic Enzymes Including Acetylcholinesterase, Butyrylcholinesterase, Alpha-Glycosidase of Some Compounds With Molecular Docking Study
(Taylor & Francis inc, 2021) Turkan, Fikret; Taslimi, Parham; Abdalrazaq, Sakar Mubarak; Aras, Abdulmelik; Erden, Yavuz; Celebioglu, Hasan Ufuk; Gulcin, Ilhami
Inhibitory effect of the complexes on some metabolic enzyme demonstrated that the enzymes inhibited by ligand and it's complex molecules at the micromolar level. The best inhibition effect for alpha-glycosidase (alpha-Gly) enzyme against cobalt complex with Ki value of 3.77 +/- 0.58 mu M. For achethylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes against SM-Co complex, Ki values of 74.23 +/- 5.02 mu M and 101.21 +/- 12.84 mu M Ki were observed, respectively. Molecular docking studies were performed to compare the biological activities of ligands and ligand complexes against enzymes whose names are AChE for ID 4M0E, BChE for ID 5NN0, alpha-Gly for ID 1XSI respectively. Also, anticancer properties of the complexes studied. The doses of all compounds caused significant reductions in MCF-7 cell viability. Zr compound showed the best cytotoxic activity against the MCF-7 cell. SM ligand administered to PC-3 cells exhibited a more pronounced cytotoxic effect than the SM-Co and Zr compounds. Communicated by Ramaswamy H. Sarma
The Effects of Some Antibiotics From Cephalosporin Groups on the Acetylcholinesterase and Butyrylcholinesterase Enzymes Activities in Different Tissues of Rats
(Taylor & Francis Ltd, 2019) Turkan, Fikret; Huyut, Zubeyir; Taslimi, Parham; Gulcin, Ilhami
In our study, it was aimed to investigate the effects of cefazolin, cefuroxime, and cefoperazon injected to rats on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzyme activities in the heart, brain, eye, liver, and kidney tissues of rats. Liver AChE activity at the 1st and 3rd hours of cefuroxime groups was higher than the control group at the same time (p <.05). The AChE activity of the heart tissue decreased in the cefazolin group compared to the control group at the same hour, whereas it increased in the cefuroxime group (p <.05). AChE activities of kidney tissue of cefazolin and cefuroxime groups were lower than those of the same control group on the 3rd and started to increase on the next hours (p <.05). BChE activity is measured in tissues increased within the first three hours and decreased significantly within the first hour in the cefoperazone group (p <.05).
The in Vivo Effects of Cefazolin, Cefuroxime, and Cefoperazon on the Carbonic Anhydrase in Different Rat Tissues
(Wiley, 2018) Turkan, Fikret; Huyut, Zubeyir; Taslimi, Parham; Gulcin, Ilhami
In this paper, the in vivo effects of some antibiotics including cefazolin, cefuroxime, and cefoperazon, on the activity of the carbonic anhydrase enzyme (CA) in heart, brain, eye, liver, and kidney tissues of rats were evaluated. For this purpose, 16 different groups, which each containing six rats (n = 6), were formed (control group, cefazolin groups, cefuroxime groups, and cefoperazon groups). The rats were necropsied 60 min after the intraperitoneal injection of the chemicals into the rats. The CA activities were measured for each tissue using esterase activity methods. The activity values for each tissue obtained were statistically calculated. The CA activities in the liver tissue were assessed, and the activities of the cefoperazon groups were decreased compared to the sham groups from the third hour (p<0.05). In the cefuroxime and cefoperazon groups, the CA activities in the eye tissue were decreased during the first 3 h and then increased (p<0.05).
Investigation of the Effects of Cephalosporin Antibiotics on Glutathione S-Transferase Activity in Different Tissues of Rats in Vivo Conditions in Order To Drug Development Research
(Taylor & Francis Ltd, 2020) Turkan, Fikret; Huyut, Zubeyir; Taslimi, Parham; Huyut, Mehmet Tahir; Gulcin, Ilhami
Glutathione S-transferases are multifunctional enzymes for the cellular defense against xenobiotics and provide protection for organism. In this study, the inhibition effects of some antibiotics were investigated against GST obtained from albino-rats kidney, liver, and heart tissues. Ninety-six albino-rats were randomly divided into 16 groups (n:6). The first four groups were control groups that were administrated blank enjection and decapitated at 1-7 h. The other groups were administrated the antibiotics. In all tissues, GST activity was increased in antibiotics groups at 1st and 3rd hours compared to control groups, while it began to fall at 5th and 7th hours (p < .05). In kidney tissues, it was lower than the same control group the cefuroxime and cefoperazone groups at 7th hours (p < .05). In addition, almost all antibiotic groups of kidney tissues had higher GST activity at all hours than those of control groups, but it was higher only at 5th hours in heart tissues (p < .05).
Metal Contained Phthalocyanines With 3,4-Dimethoxyphenethoxy Substituents: Their Anticancer, Antibacterial Activities and Their Inhibitory Effects on Some Metabolic Enzymes With Molecular Docking Studies
(Taylor & Francis inc, 2022) Taslimi, Parham; Turkan, Fikret; Gungordu Solgun, Derya; Aras, Abdulmelik; Erden, Yavuz; Celebioglu, Hasan Ufuk; Gulcin, Ilhami
The compounds (3-6) used in this study were re-synthesized in accordance with our previous study. The inhibitory effect of the complexes on some metabolic enzymes was examined and it was demonstrated that the enzymes inhibited by ligands and their complex molecules at micromolar level. The best Ki value for alpha-glycosidase enzyme was absorved 1.01 +/- 0.08 mu M for compound 6. The biological activity of ligand and metal complexes against enzymes was compared with molecular docking method. The enzymes used against ligand and metal complexes respectively: Achethylcholinesterase for ID 4M0E (AChE), butyrylcholinesterase for ID 5NN0 (BChE), alpha-glycosidase for ID 1XSI (alpha-Gly). ADME analysis was performed to examine the drug properties of the compounds (3-6). Besides, the anticancer properties of the complexes were studied. The doses of all compounds caused significant reductions in MCF-7 cell viability. The 3 and 5 compounds administered to PC-3 cells exhibited a more pronounced cytotoxic effect than the other two compounds (4 and 6). Furthermore, antibacterial activities of these compounds against Escherichia coli and Staphylococcus aureus were examined. Communicated by Ramaswamy H. Sarma
Mono- or Di-Substituted Imidazole Derivatives for Inhibition of Acetylcholine and Butyrylcholine Esterases
(Academic Press inc Elsevier Science, 2019) Kuzu, Burak; Tan, Meltem; Taslimi, Parham; Gulcin, Ilhami; Taspinar, Mehmet; Menges, Nurettin
Mono- or di-substituted imidazole derivatives were synthesized using a one-pot, two-step strategy. All imidazole derivatives were tested for AChE and BChE inhibition and showed nanomolar activity similar to that of the test compound donepezil and higher than that of tacrine. Structure activity relationship studies, docking studies to on X-ray crystal structure of AChE with PDB code 1B41, and adsorption, distribution, metabolism, and excretion (ADME) predictions were performed. The synthesized core skeleton was bound to important regions of the active site of AChE such as the peripheral anionic site (PAS), oxyanion hole (OH), and anionic subsite (AS). Selectivity of the reported test compounds was calculated and enzyme kinetic studies revealed that they behave as competitive inhibitors, while two of the test compounds showed noncompetitive inhibitory behavior. ADME predictions revealed that the synthesized molecules might pass through the blood brain barrier and intestinal epithelial barrier and circulate freely in the blood stream without binding to human serum albumin. While the toxicity of one compound on the WS1 (skin fibroblast) cell line was 1790 mu M, its toxicity on the SH-SY5Y (neuroblastoma) cell line was 950 mu M.
Pyrazole[3,4-D]pyridazine Derivatives: Molecular Docking and Explore of Acetylcholinesterase and Carbonic Anhydrase Enzymes Inhibitors as Anticholinergics Potentials
(Academic Press inc Elsevier Science, 2019) Taslimi, Parham; Turkan, Fikret; Cetin, Adnan; Burhan, Hakan; Karaman, Muhammet; Bildirici, Ishak; Sen, Fatih
Recently, the pyridazine nucleus has been widely studied in the field of particular and new medicinal factors as drugs acting on the cardiovascular system. Additionally, a number of thienopyridazines have been claimed to possess interacting biological macromolecules and pharmacological activities such as NAD(P)H oxidase inhibitor, anticancer, and identified as a novel allosteric modulator of the adenosine A1 receptor. The literature survey demonstrates that coumarin, 1,2-pyrazole benzothiazole, and 1,3- thiazole scaffolds are the most versatile class of molecules. In this study, a series of substituted pyrazole[3,4-d]pyridazine derivatives (2a-n) were prepared, and their structures were characterized by Mass analysis, NMR, and FT-IR. These obtained pyrazole [3,4-d]pyridazine compounds were very good inhibitors of the carbonic anhydrase (hCA I and II) isoenzymes and acetylcholinesterase (AChE) with K-i values in the range of 9.03 +/- 3.81-55.42 +/- 14.77 nM for hCA I, 18.04 +/- 4.55-66.24 +/- 19.21 nM for hCA II, and 394.77 +/- 68.13-952.93 +/- 182.72 nM for AChE, respectively. The possible inhibition mechanism of the best-posed pyrazole[3,4-d]pyridazine and pyrazole-3-carboxylic acid derivatives and their interaction with catalytic active pocket residues were determined based on the calculations.
Synthesis and Biological Evaluation of Aminomethyl and Alkoxymethyl Derivatives as Carbonic Anhydrase, Acetylcholinesterase and Butyrylcholinesterase Inhibitors
(Taylor & Francis Ltd, 2017) Gulcin, Ilhami; Abbasova, Malahat; Taslimi, Parham; Huyut, Zubeyir; Safarova, Leyla; Sujayev, Afsun; Supuran, Claudiu T.
Compounds containing nitrogen and sulfur atoms can be widely used in various fields such as industry, medicine, biotechnology and chemical technology. Therefore, the reactions of aminomethylation and alkoxymethylation of mercaptobenzothiazole, mercaptobenzoxazole and 2-aminothiazole were developed. Additionally, the alkoxymethyl derivatives of mercaptobenzoxazole and 2-aminothiazole were synthesized by a reaction with hemiformals, which are prepared by the reaction of alcohols and formaldehyde. In this study, the inhibitory effects of these molecules were investigated against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) enzymes and carbonic anhydrase I, and II isoenzymes (hCA I and II). Both hCA isoenzymes were significantly inhibited by the recently synthesized molecules, with Ki values in the range of 58-157 nM for hCA I, and 81-215 nM for hCA II. Additionally, the Ki parameters of these molecules for BChE and AChE were calculated in the ranges 23-88 and 18-78 nM, respectively.
Synthesis and Investigation of the Conversion Reactions of Pyrimidine-Thiones With Nucleophilic Reagent and Evaluation of Their Acetylcholinesterase, Carbonic Anhydrase Inhibition, and Antioxidant Activities
(Wiley, 2018) Taslimi, Parham; Sujayev, Afsun; Turkan, Fikret; Garibov, Emin; Huyut, Zubeyir; Farzaliyev, Vagif; Gulcin, Ilhami
The conversion reactions of pyrimidine-thiones with nucleophilic reagent were studied during this scientific research. For this purpose, new compounds were synthesized by the interaction between 1,2-epoxy propane, 1,2-epoxy butane, and 4-chlor-1-butanol and pyrimidine-thiones. These pyrimidine-thiones derivatives (A-K) showed good inhibitory action against acetylcholinesterase (AChE), and human carbonic anhydrase (hCA) isoforms I and II. AChE inhibition was in the range of 93.1 +/- 33.7-467.5 +/- 126.9nM. The hCA I and II were effectively inhibited by these compounds, with K-i values in the range of 4.3 +/- 1.1-9.1 +/- 2.7nM for hCA I and 4.2 +/- 1.1-14.1 +/- 4.4nM for hCA II. On the other hand, acetazolamide clinically used as CA inhibitor showed K-i value of 13.9 +/- 5.1nM against hCA I and 18.1 +/- 8.5nM against hCA II. The antioxidant activity of the pyrimidine-thiones derivatives (A-K) was investigated by using different in vitro antioxidant assays, including Cu(2+)and Fe(3+)reducing, 1,1-diphenyl-2-picrylhydrazyl (DPPH center dot) radical scavenging, and Fe(2+)chelating activities.
Synthesis of New Cyclic Thioureas and Evaluation of Their Metal-Chelating Activity, Acetylcholinesterase, Butyrylcholinesterase, and Carbonic Anhydrase Inhibition Profiles
(Wiley, 2017) Taslimi, Parham; Sujayev, Afsun; Garibov, Emin; Nazarov, Nazar; Huyut, Zubeyir; Alwasel, Saleh H.; Gulcin, Ilhami
In the presence of trifluoracetic acid (TFAA), an efficient method for the synthesis of tetra(hexa)hydropyrimidinethione-carboxylates has been used on the basis of three-component condensation of thiourea with its different aldehydes and -diketones. Some novel cyclic thioureas were synthesized, and their hCA I, hCA II, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) inhibitors and metal-chelating properties were evaluated. K-i values of novel synthesized compounds for AChE and BChE are in the range of 51.84-135.96 and 143.96-274.55 nM, respectively. Also, HCA I and II were effectively inhibited by these novel compounds, with K-i values in the range of 404.16-745.13 nM for hCA I and of 434.20-689.57 nM for hCA II, respectively. Additionally, acetazolamide (AZA), clinically used as a CA inhibitor, with a K-i value of 883.68 +/- 121.27 nM in hCA I and 1008.66 +/- 144.70 nM in hCA II. Also, tacrine inhibited AChE and BChE showed K-i values of 314.63 +/- 31.66 and 373.57 +/- 75.07 nM, respectively.
Synthesis of Zinc Phthalocyanine Complex Containing Tetra Propanoic Acid Groups: Electronic Properties and Inhibitory Effects on Some Metabolic Enzymes
(Elsevier, 2024) Solgun, Derya Gungordu; Sadeghian, Nastaran; Taslimi, Parham; Taskin-Tok, Tugba; Agirtas, Mehmet Salih
In the new study, first the synthesis and characterization of 2, 10, 16, 24-Tetrakis-3-(phenoxy) propanoic acid phthalocyaninato zinc (II)(4) and its starting compound are presented. The aggregation properties of compound (4) were investigated with the UV-visible spectrum, and the excitation and emission properties were investigated with the fluorescence spectra. The new compounds were characterized by IR, UV-visible, Mass and 1H NMR spectroscopy. These 3-(3,4-dicyanophenoxy) propanoic acid (3) and compound (4) had effective inhibition against alpha-glycosidase, alpha-amylase, butyrylcholinesterase and acetylcholinesterase. IC50 values were found as 4.21-6.57 mu M for AChE, 0.32-1.88 mu M for BChE, 47.14-62.07 mu M for alpha-amylase, and 13.41-21.82 mu M for alpha-glycosidase. By molecular docking study, compared to reference compounds (tacrine and acarbose) of compound (4) [-9.25 kcal/mol for AChE; -9.30 kcal/mol for BChE; -6.50 kcal/mol for alpha-amylase and -8.49 kcal/mol for alpha-glycosidase seem to be more effective and promising. Drug development for the treatment of diabetes, hyperglycemia, and obesity has as one of its design goals the creation of molecules that are alpha-amylase and alpha-glycosidase inhibitors. As a result, compound (4) can have promising anti Alzheimer drug potential and record as novel anti-diabetic inhibitors.
Synthesis of Zinc Phthalocyanine Containing 1,2-Phenylene Bis (3-Chloropropanoate) Substituted Groups and Investigation of Their Metabolic Enzyme Inhibitory Effects
(Pergamon-elsevier Science Ltd, 2024) Solgun, Derya Gungordu; Sadeghian, Nastaran; Taslimi, Parham; Taskin-Tok, Tugba; Agirtas, Mehmet Salih
In this study, 4,5-dicyano-1,2-phenylene dinicotinate compound was obtained as a result of the reaction of 4,5dichlorophthalonitrile and nicotinic acid. This compound was reacted with the zinc chloride salt to obtain the original zinc phthalocyanine compound bearing 1,2-phenylene bis(3-chloropropanoate) substituted groups. This compound and its starting material were characterized with the assist of 1 H NMR, IR, UV-vis, Mass spectrum. In the docking study of compounds (3) 3 ) and (4) 4 ) against each target (AChE, BChE, alpha-Amy and alpha-Gly), Zn complex (4) 4 ) exhibits more binding affinity with the target models considered compared to ligand structure (3). 3 ). Especially, AChE protein and complex (4) 4 ) form the best binding affinity with a binding energy value of-10.55 kcal/mol. They are compatible and supportive with the data obtained as a result of in vitro analysis. These 4,5-dicyano-1,2phenylene dinicotinate (3) 3 ) and 2, 10, 16, 24 - tetrakis 1,2-phenylene bis(3-chloropropanoate) phthalocyaninato) zinc(II) (4) 4 ) complexes had effective inhibition against alpha-glucosidase, alpha-amylase, butyrylcholinesterase and AChE. Also, IC50 50 amounts were found as 7.84 and 12.36 mu M for AChE, 3.80 and 4.56 mu M for BChE, 27.08 and 38.14 mu M for alpha-amylase, and 5.30 and 9.73 mu M for alpha-glucosidase.
Synthesis, Fluorescence, Enzymes Effects, and Evaluation of Tetrahydroxy Substituted Zinc Phthalocyanine as Multitarget Metabolic Enzyme Inhibitors With Molecular Docking: the Biochemistry-Oriented Drug Design
(Springer, 2024) Solgun, Derya Gungordu; Sadeghian, Nastaran; Taskin-Tok, Tugba; Agirtas, Mehmet Salih; Taslimi, Parham
Synthesis and properties of tetrahydroxy substituted zinc phthalocyanine is reported. UV-Visible spectrum for the aggregation properties of the compound and fluorescence properties were examined by excitation, emission spectra. This complex was an inhibitor of butyrylcholinesterase (BChE), alpha-Gly, alpha-Amy, and acetylcholinesterase (AChE) enzymes for tetra- hydroxy phthalocyaninato zinc (II) 3 with IC50 values of 49.18 mu M for alpha-Amy, 110.85 mu M for BChE, 35.13 mu M for alpha-glycosidase and 54.63 mu M for AChE, respectively. On the otherside, within the scope of computational study, in vitro activity behavior and states of the related complex, which cannot be explained experimentally, were evaluated at atomic level. The pharmacodynamics properties of the complex (3) were elucidated by molecular docking against four target enzymes, AChE, BChE, alpha-Gly and alpha-Amy. After that, its potential drug candidate was investigated based on its pharmacokinetic properties with help of in silico-ADMET analysis. As a result of all the applications, a desired goal in medicinal chemistry was to develop new, reliable and safe cholinesterase and alpha-glycosidase inhibitors with high efficacy.