Ahmet Cetin

Molecular structure and vibrational bands and chemical shift assignments of 4-allyl-5-(2-hydroxyphenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione by DFT and ab initio HF calculations

The title molecule, 4-allyl-5-(2-hydroxyphenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (C(11)H(11)N(3)OS), was synthesized and characterized by IR-NMR spectroscopy and single-crystal X-ray diffraction. The compound crystallizes in the monoclinic space group is P2(1)/c, a=9.0907(5)A, b=9.1288(7)A, c=13.6222(7)A, alpha=90 degrees , beta=98.442 (4), gamma=90 degrees and V=2683.7(6)A(3), F(000)=488, D(x)=1.386 g/cm(3). In addition to the molecular geometry from X-ray experiment, the molecular geometry, vibrational frequencies, gauge including atomic orbital (GIAO) (1)H and (13)C chemical shift values of the title compound in the ground state have been calculated using the Hartree-Fock (HF) and density functional method (DFT/BLYP and DFT/B3LYP) with 6-31G(d) basis set. To determine conformational flexibility, molecular energy profile of the title compound was obtained by HF/6-31G(d) calculations with respect to selected degree of torsional freedom, which was varied from -180 degrees to +180 degrees in steps of 10 degrees . Besides, molecular electrostatic potential (MEP), frontier molecular orbitals (FMO), and several thermodynamic properties were performed by the HF and DFT methods.

Interaction of carbonic anhydrase isozymes I, II, and IX with some pyridine and phenol hydrazinecarbothioamide derivatives.

A series of hydrazinecarbothioamide derivatives incorporating ethyl, phenyl, tolyl, benzyl, and allyl moieties were prepared and tested as possible inhibitors of three members of the pH regulatory enzyme family, carbonic anhydrase (CA; EC 4.2.1.1). The inhibitory and activatory potencies of the compounds against the cytosolic human isoforms hCA I and hCA II and the transmembrane, tumor-associated hCA IX were analyzed by a hydrase assay with CO2 as substrate, and the inhibition constants (KI) were calculated. Most compounds investigated here exhibited nanomolar or low micromolar inhibition constants against the three isoenzymes. KI values were in the range of 34.1-871 nM for hCA I and compounds 5-10 showed interesting activation of the hCA II with KA value of 0.81-12.5 μM. Compounds 11-16 exhibited moderate inhibition effects on hCA IX in the range of 0.317-1.245 μM but they were less effective for hCA II. Tested compounds were also investigated using in silico applications at the binding pockets of these three targets. The different mechanisms of inhibition by these tested compounds as compared to sulfonamides, and their diverse inhibition profile for these mammalian isozymes, makes this class of derivatives of great interest for the design of novel CA inhibitors.

Investigation of acetylcholinesterase and mammalian DNA topoisomerases, carbonic anhydrase inhibition profiles, and cytotoxic activity of novel bis(α-aminoalkyl)phosphinic acid derivatives against human breast cancer

The aim of this study was to evaluate biologically active novel molecules having potentials to be drugs by their antitumor properties and by activities of apoptotic caspase and topoisomerase. Following syntheses of novel eight bis(α‐aminoalkyl)phosphinic acid derivatives (4a–h) as a result of array of reactions, compounds were evaluated by cytotoxic effects in vitro on human breast cancer (MCF‐7) and normal endothelial (HUVEC) cell lines. All phosphinic acid derivatives were effective for cytotoxicity on both MCF‐7 and HUVEC lines, while 4c, 4e, and 4f compounds were found significantly more effective. For the evaluation of antitumor properties of compounds in a highly sensitive method, their effects on inhibiting topoisomerases I and II were investigated. Also, some of the bis(α‐aminoalkyl)phosphinic acid derivatives (4a, 4e–h) showed nice inhibitory action against acetylcholinesterase and human carbonic anhydrase isoforms I and II.

6-Phenyl-3-(4-pyridyl)-1,2,4-triazolo-[3,4-b][1,3,4]thiadiazole: synthesis, experimental, theoretical characterization and biological activities.

The molecular geometry, vibrational frequencies, and gauge including atomic orbital (GIAO) (1)H and (13)C NMR chemical shift values of the title compound in the ground state have been calculated using the Hartree-Fock (HF) and density functional theory (DFT) methods with 6-31G(d) basis sets, and compared with the experimental data. The calculated results show that the optimized geometries can well reproduce the crystal structural parameters and the theoretical vibrational frequencies, and (1)H and (13)C NMR chemical shift values show good agreement with experimental data. To determine conformational flexibility, molecular energy profile of the title compound was obtained by HF/6-31G(d) and (DFT/B3LYP) calculations with respect to selected degree of torsional freedom, which was varied from -180° to +180° in steps of 10°. The energetic behavior of the title compound in solvent media was examined using the B3LYP method with the 6-31G(d) basis set by applying the Onsager and the polarizable continuum model (PCM). The results obtained with these methods reveal that the PCM method provided more stable structure than Onsagers method. The title compound has been tested in vitro for biological effects.

Evaluation as antioxidant agents of 1,2,4-triazole derivatives: effects of essential functional groups

Article history: Received on: 27/03/2015 Revised on: 08/04/2015 Accepted on: 03/05/2015 Available online: 27/06/2015 A series of 1,2,4-triazole derivative compounds substituted with groups of phenol and pyridine were synthesized in high yields and screened against several antioxidant activity parameters such as DPPH, ABTS, metal chelating, reducing power and the total antioxidant activity. The compounds showed better than expected antioxidant activity between the studied biological activity parameters. Among these, compound G(2-(5mercapto-4H-1,2,4-triazol-3-yl)phenol) had a high total antioxidant activity potential with value of 232.12±6.89 mmol/ml. Also showed fairly good ABTS cation radical and DPPH radical scavenging activity with values of IC50 = 4.59±4.19 and IC50 = 7.12±2.32μg/mL respectively. Further, the antioxidant potential of heterocyclic compounds that 1,2,4-triazole derivatives containing different functional groups were compared with various tests performed and has been shown to increase the activity of electron donating groups. Therefore, the present study demonstrates that phenol and pyridine substituted 1,2,4-triazole compounds would be a better prospective in the development of antioxidant agent.

Synthesis of some novel pyridine compounds containing bis-1,2,4-triazole/thiosemicarbazide moiety and investigation of their antioxidant properties, carbonic anhydrase, and acetylcholinesterase enzymes inhibition profiles

Some novel derivatives of thiosemicarbazide and 1,2,4‐triazole‐3‐thiol were synthesized and evaluated for their biological activities. The title compounds were prepared starting from readily available pyridine‐2,5‐dicarboxylic acid. The reaction carboxylic acid with absolute ethanol afforded the corresponding dimethyl pyridine‐2,5‐dicarboxylate (1). The reaction of dimethyl‐2,5‐pyridinedicarboxylate (1) with hydrazine hydrate good yielded pyridine‐2,5‐dicarbohydrazide (2). Refluxing compound 2 with alkyl/aryl isothiocyanate derivatives for 3–8 h afforded 1,4‐disubstituted thiosemicarbazides (3a–e). Base‐catalyzed intra‐molecular dehydrative cyclization of these intermediates furnished the 4,5‐disubstituted bis‐mercaptotriazoles (4a–e) in good yield (85%–95%). Among the target compounds, 2,2′‐(pyridine‐2,5‐diyldicarbonyl)bis[N‐(p‐methoxyphenyl)hydrazinecarbothioamide] (3c) showed very high activity with value of 72.93% against 1,1‐diphenyl‐2‐picrylhydrazyl free radical at the concentration of 25 μg/mL. The inhibitory effects of the target compounds against acetylcholinesterase (AChE), hCA I, and II were studied. AChE, cytosolic hCA I and II isoforms were potently inhibited by synthesized these derivatives with Kis in the range of 3.07 ± 0.76–87.26 ± 29.25 nM against AChE, in the range of 1.47 ± 0.37–10.06 ± 2.96 nM against hCA I, and in the range of 3.55 ± 0.57–7.66 ± 2.06 nM against hCA II, respectively.

6-Phenyl-3-(4-pyridyl)-1,2,4-triazolo-[3,4-b][1,3,4]thiadiazole

The title compound, C(14)H(9)N(5)S, has been synthesized and characterized both spectroscopically and structurally. The triazolo-thiadiazole system, the pyridine ring and the phenyl ring are all planar. The plane of the triazolo-thiadiazole system forms dihedral angles of 1.53 (13) and 7.55 (12) degrees with the planes of the pyridine and phenyl rings, respectively. In the molecule, there are two intramolecular interactions of types C-H...N and C-H...S. Intermolecular C-H...N interactions involving a phenyl CH group and a triazole N atom lead to the formation of a one-dimensional chain. In the crystal structure, two types of pi-pi interactions affect the packing of the molecules. In addition, there are intermolecular non-bonded S...N contacts of 2.870 (2) A, which may cause steric hindrance.

4-Allyl-5-pyridin-4-yl-2,4-dihydro-3H-1,2,4-triazole-3-thione: synthesis, experimental and theoretical characterization.

The title molecule, 4-allyl-5-pyridin-4-yl-2,4-dihydro-3H-1,2,4-triazole-3-thione (C(10)H(10)N(4)S), was synthesized and characterized by IR-NMR spectroscopy and single-crystal X-ray diffraction. The compound crystallizes in the monoclinic space group is P2(1)/c, a=8.006(5)Å, b=15.363(5)Å, c=8.936(5)Å, β=104.441(5)° and V=1064.4(10)Å(3), F(000)=456, D(x)=1.362 g/cm(3). In addition to the molecular geometry from X-ray experiment, the molecular geometry, vibrational frequencies, gauge including atomic orbital (GIAO) (1)H and (13)C chemical shift values of the title compound in the ground state have been calculated using the Hartree-Fock (HF) and density functional method (DFT/B3LYP) with 6-31G(d) basis set. To determine conformational flexibility, molecular energy profile of the title compound was obtained by HF/6-31G(d) and (DFT/B3LYP) calculations with respect to selected degree of torsional freedom, which was varied from -180° to +180° in steps of 10°. Besides, molecular electrostatic potential (MEP), frontier molecular orbitals (FMO), and several thermodynamic properties were performed by the HF and DFT methods.

Synthesis and in vitro antioxidant evaluation of new bis(α-aminoalkyl)phosphinic acid derivatives

GRAPHICAL ABSTRACT ABSTRACT Diamines were added to arylaldehydes in ethanol, which resulted in corresponding diimines. Novel bis-1-aminophosphinic acid compounds were synthesized through the interaction of diimines and hypophosphorous acid. The new compounds were characterized by elemental analyses, FT-IR and 1H, 13C and 31P NMR techniques. The in vitro antioxidant activity of the newly synthesized compounds were measured and found to exhibit significantly higher antioxidant activity than the standard.

3,3′‐(Pyridine‐2,6‐di­yl)bis­(4‐allyl‐4,5‐dihydro‐1H‐1,2,4‐triazole‐5‐thione)

# 2006 International Union of Crystallography All rights reserved In the title compound, C15H15N7S2, the asymmetric unit consists of two independent molecules which differ from each other in the orientation of the allyl group. In each molecule, there are two very weak intramolecular C—H N hydrogen bonds. In the crystal structure, the two independent molecules are arranged alternately through N—H S hydrogen-bonded rings to form a molecular chain running along the [121] direction.