Browsing by Author "Bildirici, Ishak"

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Amino Acid and Dicyclohexylurea Linked Pyrazole Analogues: Synthesis, in Silico and in Vitro Studies
(Wiley-v C H verlag Gmbh, 2023) Cetin, Adnan; Donmez, Ali; Dalar, Abdullah; Bildirici, Ishak
Pancreatic lipase (PL) inhibitors have received considerable attention by several researchers because of its ability to hydrolyse the triglycerides in the small intestine. This study reports the (i) synthesize of new pyrazole derivatives binding amino acid and Dicyclohexylurea (DCU), (ii) their pharmaceutical potentials- via enzyme inhibitory activity towards PL and antioxidant activities (using complementary antioxidant methods including FCR, FRAP and ORAC), (iii) the possible interactions between pyrazole compounds and PL enzyme through in silico studies, and the pharmacokinetic properties of the tetra-substituted pyrazole analogues by PreADMET. Enzyme activities with IC50 values of the pyrazole analogues were found to be in a high range of 6.6 +/- 0.4 mu M to 13.5 +/- 0.2 mu M. However, antioxidant activities of the pyrazole analogues exhibited low binding affinities against FCR, FRAP, and ORAC. The pyrazole analogues with docking scores were in the range of -7.3 to -15.2 and their SAR analysis were demonstrated to highlight the importance of amino acid and DCU linked scaffolds. Two web tools were utilized for the purpose of predicting ADMET parameters of drugs and drug-like pyrazole analogues. These results suggested that the amino acid and DCU linked pyrazole analogues have potential as PL inhibitors.
Determination of the Enol Form of Asymmetric 1,3-Dicarbonyl Compounds: 2d Hmbc Nmr Data and Dft Calculations
(Serbian Chemical Soc, 2018) Tan, Meltem; Bildirici, Ishak; Menges, Nurettin
In this study, a series of asymmetric aryl 1,3-dicarbonyl compounds were synthesized and their enol forms were observed via experimental data and theoretical calculations. According to the H-1- and C-13-NMR results, all the investigated compounds were found as a single enol form in CDCl3 solution. Moreover, their HMBC spectra were applied to identify the observed enol forms and correlations between certain protons and carbon atoms were considered. The dihedral angles of the asymmetric compounds that have aryl units on both sides were calculated by DFT to understand the reason for the observed enol forms. Small dihedral angles caused longer conjugation, resulting in more stable compounds and it was found that the observed enol forms were based on small dihedral angles, namely, resonance is the driving force. Furthermore, the compounds possessing both aryl and alkyl moieties prefer the enol form towards the aromatic ring side due to longer conjugation.
An Entry Into Obtaining Pyrazole-, Chromone-, or Oxadiazole-Substituted 1h-Pyrazoles Via 2,3-Furandiones
(Wiley, 2013) Cam, Serkan; Bildirici, Ishak; Menges, Nurettin; Tan, Meltem; Sener, Ahmet
Some new pyrazole-, chromone-, or oxadiazole-substituted 1H-pyrazoles were obtained via 2,3-furandiones. Also, we have presented their plausible mechanisms based on rearrangement; one of these rearrangements is BakerVenkataraman.
Further Derivatives of 4-Benzoyl Acid and Their Antibacterial Activities
(Springer Birkhauser, 2007) Bildirici, Ishak; Sener, Ahmet; Tozlu, Israfil
Compound 4, 5, 6, 7, and 8 were synthesized from 4-benzoyl-1,5-diphenyl-1H-pyrazole- 3-carboxylic acid 1 as a starting material. The pyrazolo[ 4,3-d] oxazinone 4 was obtained from direct reaction of the acid 1 with hydroxylamine hydrochloride. Acid chloride 2 was converted easily into the new derivatives consisting of 1-(4-benzoyl-1,5-diphenyl-1H-pyrazol-3-oyl)-sulfamide 5 and 3,4-dibenzoyl-1,5-diphenyl-1H-pyrazole 6. The nitrile derivative 7 was obtained by dehydration of the amide 3 in a mixture of SOCl2 and Dimethylformamide (DMF). Cyclocondensation reaction of 7 with anhydrous hydrazine led to the formation of 7-aminopyrazolo[ 3,4-d] pyridazine 8 derivative. These new synthesized compounds evaluated for their antibacterial activities against Gram-positive and Gram-negative bacteria using the tube dilution method. The finding of antibacterial activity study showed that the sulfamide derivative 5 was the best compound of the series, exhibiting antibacterial activity against both Gram-positive and Gram-negative bacteria.
Gaba-At Inhibitors: Design, Synthesis, Pharmacological Characterization, Molecular Docking and Admet Studies
(Wiley-v C H verlag Gmbh, 2023) Sevincli, Zekiye Seyma; Bildirici, Nurettin; Cetin, Adnan; Bildirici, Ishak
& gamma;-aminobutyric acid (GABA) is the main neuroinhibitory transmitter and a non-proteinogenic amino acid in the brain. When the brain concentration of GABA diminishes below a threshold level, it can cause excess neuronal excitation and lead to convulsions. & gamma;-Aminobutyric acid aminotransferase (GABA-AT) is an enzyme that catalyzes the conversion of GABA to succinic semialdehyde in the GABA shunt pathway and responsible for breaking down GABA in the brain. By inhibiting GABA-AT activity, it may be possible to increase the levels of GABA in the brain and reduce the likelihood of seizures. Herein, the synthesis and evaluation of & alpha;-pyrazolo-(aryl/alkyl)methyl-ketone and pyrazolo[5,1-a]isoquinoline derivatives were carried out anticonvulsant activity, with a focusing on GABA-AT inhibition. In total, 20 novel compounds were synthesized, and characterized with binding assays at GABA-AT receptor, in the 0.060 & PLUSMN;0.01 to 5.99 & PLUSMN;0.10 micromolar range. The ADMET predictions and drug-like characteristics of & alpha;-pyrazolo-(aryl/alkyl)methyl-ketone and pyrazolo[5,1-a]isoquinoline compounds were identified by pharmacokinetic investigations. Furthermore, the predicted analogue-enzyme complexes with docking scores were in the range of -7.3 to -10.5, and their SAR analysis was found to be significant of & alpha;-pyrazolo-(aryl/alkyl)methyl-ketone and pyrazolo[5,1-a]isoquinoline structures in medicinal chemistry. Our results revealed that this new structural information will be useful for the future design and synthesis of activity-based GABA-AT inhibitors. The research presented in this manuscript is focused on the development of new high affinity ligands for GABA-AT receptor. These analogues for GABA-AT inhibitor candidates were designed using the scaffold from the pyrazole and isoquinoline by omitting the substituent in the 3,5-positions. The pharmacological profile of these analogues was determined using an in vitro method. This has aided in the design of a novel selective inhibitor for the GABA-AT receptor.image
Labelling of a Pyrazole Derivative With 131i and Investigation of Its Radiopharmaceutical Potential
(Science Press, 2013) Kurtdede, Esra; Bildirici, Ishak; Enginar, Huseyin; Sener, Ahmet
We investigated the radiolabeling efficiency, in vitro stability, and biodistribution of radioactive iodine (I-131)-labeled 4-benzoyl-1-(4-carboxyphenyl)-5-phenyl-1H-pyrazole-3-carboxylic acid (P3CA). A quality-control study of the labeled substance (I-131-P3CA) was conducted using electrophoresis and radio thin-layer chromatography (RTLC). Biodistribution studies were undertaken in 9 female albino Wistar rats. Rats were killed at various times (15, 60 and 180 min), their organs removed, and percentage of injected dose per gram (ID%/g) values calculated. The labeling yield of P3CA was 97.08%+/- 0.80%. The maximum uptake of I-131-P3CA was seen in the lungs, stomach and spleen at 15 min. The uptake of labeled compound decreased over time in the lungs, whereas that in the stomach decreased. These data suggest that I-131-P3CA had high binding efficiency, high uptake in the lung, and sufficient stability to be used in diagnostic studies.
A Novel Oligo-Pyrazole Thin Film: Synthesis, Characterization, Optical and Morphological Properties
(Springer, 2018) Cetin, Adnan; Korkmaz, Adem; Bildirici, Ishak
Pyrazole-3,4-dicarboxylic acid 2 was synthesized via the hydrolysis of pyrazole-3-carboxylic acid 1 and subsequently heated with thionyl chloride to give the novel pyrazole-3,4-dicarbonyl dichloride 3, which was easily converted into oligo-pyrazole 4 upon its reaction with p-phenylene-diamine. These newly synthesized compounds were characterized by H-1-NMR, C-13-NMR, and FT-IR spectroscopy, and gel permission chromatography (GPC). Three novel oligo-pyrazole thin films were prepared using oligo-pyrazole 4 with these respective values of thickness: 20, 21, and 24 mu m. The optical properties of the films, including the absorbance, transmittance, and optical band gap, were determined using UV-vis spectroscopy. The E (g) values of the films were found to be 1.426, 1.537, and 1.648 eV for the 20, 21, and 24 mu m thick organic films, respectively. Atomic force microscopy (AFM) was used to examine the surface morphology and properties of the organic films. In the AFM images, a few black regions were observed and several yellow regions appeared over a large area, and the surface of the oligo-pyrazole films had an extremely low roughness value. The as-synthesized oligo-pyrazole has great potential in optoelectronic applications according to the optical properties of the as-prepared films.
Novel Pyrazole-Centered Derivatives Having Mono/Di Chiral Centered Group as Organocatalyst for Henry Reaction
(Soc Chemists Technologists Madeconia, 2020) Cetin, Adnan; Bildirici, Ishak; Gumus, Selcuk
The chiral substituted pyrazole-3-carboxamides (4a-c), pyrazole-3-carboxylates (5a-c), pyrazole-3-thioureides (7a-c) and pyrazole-3,4-dicarboxamides (10a-c) were prepared via the pyrazolo-3-chlorocarbonyl 2, pyrazolo-3,4-dicarboxy methyl ester 3 with pyrazole-3-isothiocyanate 6 with different (R)-chiral amino alcohols. All of the synthesized chiral compounds binding a pyrazole skeleton were investigated as organocatalysts for asymmetric aldol reactions between nitromethane and p-nitrobenzaldehyde in the presence of CuCl. Enantiomeric excesses and the reaction yields were found to be appropriate values. Furthermore, the best organocatalyst applied in this study was identified after careful optimization of conditions. Lastly, all of the novel compounds were subjected to computational analysis at the B3LYP/6-31++G(d,p) level of theory to obtain information about their structural and electronic properties.
One Step Synthesis of Some 2,5,6-Trisubstituted
(Tubitak Scientific & Technological Research Council Turkey, 2008) Sener, Ahmet; Bildirici, Ishak; Genc, Hasan; Menges, Nurettin; Eskinoba, Siddik
A number of novel 2,5,6-trisubstituted-1,3-dioxin-4-one derivatives were synthesized via one step reactions between dibenzoylmethane or benzoylacetone and oxalyl chloride in refluxing solvents containing various aldehydes.
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.
Studies on the Different Reaction Pathways Between 3-Acetyl and Alkylamines
(Wiley-v C H verlag Gmbh, 2010) Genc, Hasan; Tan, Meltem; Gumus, Selcuk; Menges, Nurettin; Bildirici, Ishak; Sener, Ahmet
3-Acety1-5-benzoy1-6-methy1-2-pheny1-4H-pyran-4-one has been subjected to condensation with a series of primary amines (ethylamine - octylamine) to clarify the proposed mechanism in our previous study. The reactions of the shorter amines of the series (ethylamine - butylamine) yielded unsymmetric pyridinone products, whereas the other amines (pentylamine - octylamine) yielded symmetrical pyridinones. The starting material and the products as well as the intermediates have been subjected to theoretical analysis by quantum chemical calculations at B3LYP/6-3 I G(d,p) level, which provided supporting data for the experimental findings.
A Study on Chemical Behaviors of Some 4-Pyrones Synthesized by One-Step Reactions Towards Various Amines
(Wiley-blackwell, 2007) Sener, Ahmet; Eskinoba, Siddik; Bildirici, Ishak; Genc, Hasan; Kasimogullari, Rahmi
Cycloaddition of acetylbenzoyl ketene generated in situ as an intermediate during one-step reaction between excess benzoylacetone and oxalylchloride to C=C double bond of cyclic enol form of benzoylacetone gave 3-acetyl-5-benzoyl-6-methyl-2-phenyl-4(4H)-pyrone 1a. Condensation reactions of la together with 3,5-dibenzoyl-2,6-diphenyl-4(4H)-pyrone 1b and 3-benzoyl-5-ethoxycarbonyl-2,6-diphenyl-4(4H)-pyrone 1c with two-fold excess primary amines provided a series of 3-benzoyl-1-alkyl-5-(1-alkylimino-ethyl)-6-phenyl-2-methyl-4(1H)-pyridinone 2, 3,5-dibenzoyl-1-alkyl-2,6-diphenyl-4(1H)pyridinone 3a-c and 3-benzoyl-1-alkyl-5-ethoxycarbonyl-2,6-diphenyl-4(1H)-pyridinone 3d,e derivatives, respectively. In addition, while prolonged reaction of n-pentylamine with unsymmetrical pyrone derivative la gives a symmetrical pyridinone derivative namely 3,5-dibenzoyl-2,6-dimethyl-1-pentyl-4(1H)pyridinone 5, much prolonged action n-pentylamine and then aqueous n-pentylamine on 1b resulted in degradation of the 4-pyrone ring to give dibenzoylmethane.
A Study on Synthesis and Antimicrobial Activity of 4-Acyl
(Elsevier Science Bv, 2018) Cetin, Adnan; Bildirici, Ishak
4-Acyl-pyrazole-3-carboxylic acids (1) were synthesized via the reaction of 4-acyl-2,3-furandiones (F) with hydrazone (1-benzylidene-2-(2,5-dimethyl-phenyl)-hydrazine) by heating under solid phase and their acid chlorides (2) were obtained. Then these derivatives were easily converted into the corresponding derivatives such as ester, amide, ureide, pyrazolo-pyridazine, etc. Totally 62 new compounds were synthesized. The structures of these new synthesized compounds were determined by spectroscopic methods and the in vitro antibacterial activity of newly synthesized compounds were carried out against some gram-positive and gram-negative bacteria by well diffusion method (zone inhibition). Our results have showed that these new synthesized compounds have much potent of antibacterial activity owing to containing of pyrazole and/or pyridazine, chromone, oxazine, furane, and pyrrole rings. Some of the new pyrazole derivatives exhibited higher activities than reference drugs against the representative bacteria. (C) 2016 King Saud University. Production and hosting by Elsevier B.V.
Synthesis and Antibacterial Activity of 4-Benzoyl Acid and Derivatives
(Springer Birkhauser, 2009) Bildirici, Ishak; Sener, Ahmet; Atalan, Ekrem; Battal, Abdulhamit; Genc, Hasan
A new 1H-pyrazole-3-carboxylic acid 2, along with hydrazono-pyridazinone 3, a by-product, and its derivatives 4-7 were synthesized and the structures confirmed by infrared (IR) and H-1 and C-13 nuclear magnetic resonance (NMR) data. These new compounds were evaluated for their antibacterial activities against Gram-positive and Gram-negative bacteria using the tube dilution method. The minimal inhibitory concentrations (MICs) experiments revealed that most compounds exerted inhibitor effects against Klebsiella pneumonia, Escherichia coli, Bacillus subtilus, and Xanthomonas compestris test microorganisms. Moreover, the results showed that the pyrazolo[3,4-d]pyridazine compounds were the best compounds of the series, exhibiting antibacterial activity against both Gram-positive and Gram-negative bacteria.
Synthesis and Evaluation of Aromaticity and Tautomerization of Pyrazolopyridazin(On)es
(indian Acad Sciences, 2017) Menges, Nurettin; Bildirici, Ishak
Aromaticity of pyrazolopyridazin(on)es was investigated using NICS(0), NICS(1), NICSzz(1), FIPC-NICS and HOMA aromaticity indexes and it was observed that aromaticity of pyridazin(on)es was amenable to aromaticity of pyrazole and vice versa. Some tautomeric forms of pyridazinone were analyzed and the localized orbital locator maps, electron density maps, Fuzzy, Laplacian, and Mayer bond order methods showed dominant form. Different substituents, amine, chlorine, phenyl, methyl, hydrogen, substituted-phenyl, etc. on both the rings were chosen to search out the substituent effect. Aromaticity of pyrazolopyridazin(on)es was searched out in detail for the first time.
Synthesis and Sar Studies of Pyrazole-3 And-3 Thioureides Including Chiral Moiety: Novel Candidates as Antibacterial Agents
(Serbian Chemical Soc, 2018) Bildirici, Ishak; Cetin, Adnan; Menges, Nurettin; Alan, Yusuf
A series of tetrasubstituted pyrazole-3-carboxamides (3a-c) and pyrazole-3-carbonyl thioureides (6a-c) were synthesized and their structures characterized by IR, NMR and elemental analysis. The antibacterial potential against specific Gram-positive and Gram-negative strains and the antifungal activities of all novel compounds were investigated. Structure-activity relationships (SAR) studies and some theoretical parameters (ClogP, CMR, PSA and ESP) of the compounds were performed on these two pyrazole derivatives. Pyrazole-3-carboxylate ester 2 was used for the synthesis of the carboxamide derivatives. The reactions of pyrazole-3-carbonyl isothiocyanate 5 with appropriate chiral amino alcohols were utilized for synthesizing the thioureide derivatives. Both of these types of pyrazole derivatives including a chiral moiety exhibited pronounced antibacterial activities. According to the present in vitro study, some of the promising compounds might be new candidates for a new generation of antibacterial drugs.
Synthesis and Some Reactions of 4-(ethoxycarbonyl) Acid
(Wiley, 2007) Sener, Ahmet; Tozlu, Israfil; Genc, Hasan; Bildirici, Ishak; Arisoy, Kadir
1,5-Diphenyl-1H-pyrazole-3,4-(dicarboxylic acid-4-ethyl ester 2, obtained from the 4-ethoxycarbonyl-5phenyl-2,3-furandione 1 and N-benzylidene-N'-phenyl hydrazine, was converted via reactions of its acid chloride 3 with various alcohols or N-nucleophiles into the corresponding ester 5 or amide derivatives 6, respectively. In addition, 2 was decarboxylated to give ethyl 1,5-diphenylpyrazole-4-carboxylate 4. Nitrile 7 derivative of 2 was also obtained by dehydration of 6a in a mixture of SOCl2 and DMF. While cyclo condensation reaction of 2 with hydrazine hydrate leads to the formation of pyrazolo[3,4d]pyridazine-4,7-dione 8, the reaction of 3 with anhydrous hydrazine provided a new bis pyrazole derivative 9.
Tetra-Substituted Pyrazole Analogues: Synthesis, Molecular Docking, Admet Prediction, Antioxidant and Pancreatic Lipase Inhibitory Activities
(Springer Birkhauser, 2023) Cetin, Adnan; Donmez, Ali; Dalar, Abdullah; Bildirici, Ishak
The development of novel analogues for the pancreatic lipase (PL) inhibitors and antioxidant candidates remains a significant research objective, as these studies are essential to our understanding of the role of PL receptor in obesity. Herein, we report on the synthesis, molecular docking, absorption, distribution, metabolism, excretion and toxicity (ADMET) properties, and biological evaluation of ten tetra-substituted pyrazole analogues as agents of PL inhibitors and antioxidant activities. The tetra-substituted pyrazole analogues displayed good binding affinity against Folin-Ciocalteu Reducing (FCR), Ferric Reducing Antioxidant Power (FRAP). However, the synthesized analogues displayed low binding affinity against Oxygen Radical Absorbance Capacity (ORAC). The tetra-substituted pyrazole analogues exhibited effective PL inhibition in the range of 2.0 +/- 0.0 and 34.3 +/- 0.3 mu M according to the enzyme assays. Furthermore, the detailed interactions and binding energies of the PL-tetra-substituted pyrazole analogues' complexes were determined using molecular docking studies. The binding energies of the PL-tetra-substituted pyrazole analogues' complexes were found in range of -9.4 to -13.2 kcal/mol. In addition, the ADMET predictions of tetra-substituted pyrazole analogues were carried out using PreADMET software. Overall, the obtained results revealed that antioxidant and PL inhibitory activities of tetra-substituted pyrazole analogues were in consensus with the ADMET predictions results.
Unraveling the Synthesis, Characterization, and Optical Behaviors of Thin Films: a Comprehensive Study
(Springer, 2024) Cetin, Adnan; Bildirici, Ishak
Thin films have significant importance both in academia and industry due to their unique properties and wide range of applications in electronic devices, solar cells, sensors, flat panel displays, and more. The current study aimed to synthesize and characterize polymers that exhibit semiconductor behavior and investigate their potential use in optoelectronic devices. For this purpose, thin films were prepared from the synthesized polymers. The optical properties of thin films with thicknesses of 23 mu m and 4 mu m were measured using UV-Vis spectroscopy, and the Eg values were found to be 1.30 eV and 2.16 eV, respectively. Results indicated that the obtained values of the optical bandgap energy and refractive index of the thin films suggested that they can be promising materials for the fabrication of optoelectronic devices such as solar cells, sensors, and light-emitting diodes. The observed dependence of these properties on the thickness of the films also suggested that their performance can be tuned by controlling their deposition parameters. Overall, these results demonstrated the potential of thin films as versatile building blocks for various applications in the fields of photonics and electronics.
Unsymmetrical Pyrazole-Based New Semiconductor Oligomer: Synthesis and Optical Properties
(Springer, 2017) Cetin, Adnan; Gunduz, Bayram; Menges, Nurettin; Bildirici, Ishak
Poly(p-phenylene-1-(2,5-dimethylphenyl)-5-phenyl-1H-pyrazole-3,4-dicarboxyamide)(poly(PDPPD)) was synthesized from reactions of p-phenylenediamine and 1-(2,5-dimethylphenyl)-5-phenyl-1H-pyrazole-3,4-dicarbonyl dichloride (monomer) by heating under solvent. This newly synthesized poly(PDPPD) was characterized by 1 H, 13 C-NMR, FT-IR, gel permeation chromatography (GPC). In addition, we investigated optical properties of the poly(PDPPD) containing the substituted pyrazole ring at different molarities. The average transmittance (T-avg) values of the poly(PDPPD) in the visible (V) region were higher than the Tavg values in the near-ultraviolet (NU) region. The Tavg values of the poly(PDPPD) in the NU and visible (V) region decreased with increasing molarity. The absorption band edge (Absbe) value of the poly(PDPPD) decreased with increasing molarity. It was observed that the optical band gap (E-g) of the poly(PDPPD) value decreased more with increasing molarity. The refractive index of the poly(PDPPD) decreased with increasing wavelength and decreasing molarity. The structure of the poly(PDPPD) in the lowest energy was optimized by DFT calculation and its HOMO-LUMO orbitals were plotted.