Synthesis, antimicrobial activity and acid dissociation constants of methyl 5,5-diphenyl-1-(thiazol-2-yl)pyrrolidine-2-carboxylate derivatives

Nural, Yahya | Gemili, Muge | Ulger, Mahmut

In this study, a series of polysubstituted methyl 5,5-diphenyl-1-(thiazol-2-yl)pyrrolidine-2-carboxylate derivatives were designed and synthesized by the cyclization reaction of methyl 1-(benzoylcarbamothioyl)-5,5-diphenylpyrrolidine-2-carboxylates and 2-bromo-1-(4-substituted phenyl) ethanones in 70-96% yield. The starting pyrrolidine derivatives were synthesized via a 1,3-dipolar cycloaddition reaction in 83-88% yield. The stereochemistry of one of these methyl 5,5-diphenyl-1-(thiazol-2-yl)pyrrolidine-2-carboxylate derivatives was characterized by a single crystal X-ray diffraction study and the acid dissociation constants of these compounds were determined. An antimicrobial screening was performed against different bacterial and fungal strains and against the M. tuberculosis H37Rv strai...

Synthesis, Biological Evaluation, Molecular Docking, and Acid Dissociation Constant of New Bis-1,2,3-triazole Compounds

Nural, Yahya | Ozdemir, Sadin | Yalcin, Mustafa Serkan | Demir, Bunyamin

In this study, new bis-1,2,3-triazole derivatives, N,N '-(1,3-phenylene)bis(2-(4-R-1H-1,2,3-triazol-1-yl)acetamide), were synthesized by copper-catalyzed azide-alkyne cycloaddition click chemistry in 84-96 % yield. A wide range bioactivity screening was performed to determine DNA cleavage, antioxidant, antibacterial and antifungal activities. All of the synthesized bis-1,2,3-triazoles showed excellent DNA cleavage activity and 4 e, bearing 2-bromoethyl moiety as a substituent, was almost degraded all of the plasmid DNA. Molecular docking simulations suggest that the synthesized compounds act as minor groove binders of DNA. The antioxidant activities of the bis-1,2,3-triazoles were determined based on the radical scavenging effect of the stable 2,2-diphenyl-1-picrylhydrazyl (DPPH) free...

Synthesis, antimycobacterial activity, and acid dissociation constants of polyfunctionalized 3-[2-(pyrrolidin-1-yl)thiazole-5-carbonyl]-2H-chromen-2-one derivatives

Nural, Yahya

This study reports on synthesis and determination of antimycobacterial activity and acid dissociation constants of polyfunctionalized 3-[2-(pyrrolidin-l-yl)thiazole-5-carbonyl[-2H-chromen-2-one derivatives, containing thiazole, coumarin, and pyrrolidine octahydropyrrolo[3,4-c]pyrrole moieties. The products were synthesized by a cyclization reaction of 5,5-diphenylpyrrolidine N-aroylthioureas or methyl 5-substituted 4,6-dioxo-3,3-diphenyloctahydropyrrolo[3,4-c[pyrrole-lcarboxylate N-aroylthioureas and 3-(bromoacetyl)coumarin with good to excellent yield (81-97%). The compounds exhibited antimycobacterial activity against the M. tuberculosis H37Rv strain with minimum inhibitory concentration values in the range of 31.25-125 mu g/cm(3). Acid dissociation constants of the compounds were determ...

Naftokinon yapısı içeren bileşiklerin bazı metal komplekslerinin oluşum sabitlerinin belirlenmesi

Kocagöz, Gülçin

2023-04-14

Synthesis, anti-inflammatory activity, inverse molecular docking, and acid dissociation constants of new naphthoquinone-thiazole hybrids

Efeoglu, Cagla | Selcuk, Ozge | Celik, Begum | Tumkaya, Ece | Nural, Yahya

hronic Inflammation is associated with various types of diseases that involves pro-inflammatory cytokines like IL-6 and TNF-alpha. High costs and serious side effects of available anti-inflammatory/immunomodulatory drugs led us to design new compounds with promising anti-inflammatory activities. Many drugs and biologically important compounds involve naphthoquinone and thiazole moieties in their core structures. Thereby, here we report the synthesis, characterization and anti-inflammatory activities of new naphthoquinone thiazole hybrids by reaction of naphthoquinone acyl thioureas with various alpha-bromoketone derivatives. The position of NO2 group in one of the phenyl rings of naphthoquinone thiazole hybrids was changed while different substituents were introduced at the para position o...

Pt(II) and Ni(II) complexes of octahydropyrrolo[3,4-c]pyrrole N-benzoylthiourea derivatives: Synthesis, characterization, physical parameters and biological activity

Gemili, Muge | Ulger, Mahmut | Nural, Yahya

In this study, four novel Pt(II) and Ni(II) complexes of octahydropyrrolo[3,4-c]pyrrole, consisting of pyrrolidine fused to pyrrolidine-2,5-dione, N-benzoylthiourea derivatives were synthesized and their structural characterization was performed by NMR, FT-IR, MS, HRMS and elemental analysis techniques and single crystal X-ray diffraction studies. The octahydropyrrolo[3,4-c]pyrrole N-benzoylthiourea compound 3c crystallizes triclinic, with space group P-1. Pt(II) and Ni(II) ions created cis-complexes Pt(II) 4c and Ni (II) 5a forming distorted square-planar structures in orthorhombic space groups Pnma and Pbca, respectively. Furthermore, the ligands behave as bidentate and bind to the metal atom via the S and O atoms. Acid dissociation constants of the ligands were determined by potentiomet...

Potansiyel biyoaktif polisübstitüe tiyohidantoin türevi yeni bileşiklerin eldesi, karakterizasyonu ve iyonlaşma sabitlerinin belirlenmesi

Poyraz, Samet

New naphthoquinone-imidazole hybrids: Synthesis, anion recognition properties, DFT studies and acid dissociation constants

Nural Yahya

The two new naphthoquinone-imidazole based dyes containing indole and pyrene moiety were synthesized and their molecular structures were confirmed by FT-IR, H-1/C-13 NMR, and HRMS. The anion selectivity and sensitivity of dyes were studied with selected TBA salts in DMSO and binary mixture DMSO:Water (1:1, v/v). These interaction mechanisms were verified by spectrophotometric, spectrofluorometric, and H-1 NMR titration methods. While the both dyes interact with F-, AcO-, CN-, and H2PO4- in DMSO, only CN- interact with dyes in the aqueous solution. In addition, the experimental results were explained by DFT calculations. The acid dissociation constants of the dyes were determined in 25.0 +/- 0.1 degrees C, 0.1 M NaCl ionic strength in 40% (v/v) DMSO-Water aqueous solution, and acid dissocia...

Synthesis, Enzyme Inhibition, and Acid Dissociation Constant of 1,4-Naphthoquinone Thiazole Hybrid

Nural, Yahya

In this study, N-((Z)-4-((3r,5r,7r)-adamantan-1-yl)-3-(3-amino-1,4-dioxo-1,4-dihydronaphthalen-2yl)thiazol-2(3H)-ylidene)-2,6-difluorobenzamide 3 was synthesized as a new 1,4-naphthoquinone thiazole hybrid compound by reaction of naphthoquinone acyl thiourea compound 2 with 1-((3r,5r,7r)-adamantan-1-yl)-2-bromoethan-1-one in 74% yield and its molecular structure was characterized by various analytical techniques such as 1H/13C NMR, FT-IR, and HRMS. The inhibition effect of the synthesized compound on butyrylcholinesterase (BChE), acetylcholinesterase (AChE), and human carbonic anhydrase isoenzymes (hCA I and hCA II) was investigated. The product 3 showed varying degrees of inhibition 89.92 ± 10.47 nM (against hCA I), 51.60 ± 5.37 nM (against hCA II), 68.11 ± 6.58 nM (against AChE), and 126...

Naphthoquinone–thiazole hybrids bearing adamantane: Synthesis, antimicrobial, DNA cleavage, antioxidant activity, acid dissociation constant, and drug-likeness

Ozdemir, Sadin | Yalçın, Mustafa Serkan | Nural, Yahya

In this study, four novel naphthoquinone–thiazole hybrids bearing adamantane were synthesized by reaction of naphthoquinone–aroylthiourea derivatives with 1-adamantyl bromomethyl ketone in 75-85% yield and were characterized using 1H/13C NMR, FT-IR, and HRMS techniques. Various biological activities of the synthesized compounds, such as antibacterial, antifungal, DNA cleavage, and antioxidant activities, were screened. The compounds showed antibacterial activity against Escherichia coli, Bacillus cereus, Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus hirae, and Legionella pneumophila subsp. pneumophila strains with MIC values in the range of 4–64 µg/mL and antifungal activity against Candida albicans strains with MIC values in the range of 16–64 µg/mL. The compounds had DNA cl...

1,4-Naphthoquinone thiazoles: Synthesis, crystal structure, anti-proliferative activity, and inverse molecular docking study

Efeoglu, Cagla | Demir, Bunyamin | Yabalak, Erdal | Nural, Yahya

In this study, 1,4-naphthoquinone thiazole hybrids were synthesized by reacting 1,4-naphthoquinone thioureas with various alpha-bromoketones in 78-86 % yields and characterized using 1H NMR, 13C NMR, FT-IR, and HRMS techniques. Furthermore, single crystal x-ray diffraction studies were also performed for 3b and 3c hybrids to determine stereochemistry. Density Functional Theory (DFT) calculations were performed to obtain additional information and to support the x-ray studies. The in vitro anti-proliferative activities of 1,4-naphthoquinone thiazoles were investigated against PC3 human prostate cancer cells. The products 3a-h showed antiproliferative activity against PC3 cells, and the cell viability studies showed that the IC50 values of compounds 3f and 3e were 20.10 mu M and 21.14 mu M, ...

Polysubstituted pyrrolidines linked to 1,2,3-triazoles: Synthesis, crystal structure, DFT studies, acid dissociation constant, drug-likeness, and anti-proliferative activity

Ince, Tuncay | Demir, Bunyamin | Erat, Selma | Nural, Yahya

Novel pyrrolidines linked to 1,2,3-triazole derivatives, dimethyl 1-(2 (4-R-1H 1,2,3 triazol-1-yl)-acetyl)-5,5-diphenylpyrrolidine-2,4-dicarboxylate, were synthesized in the presence of sodium ascorbate and copper (II) sulfate pentahydrate by click chemistry in excellent 89-95% yield. The H-1 NMR, C-13 NMR, DEPT, COSY, HMQC, FT-IR, HRMS and elemental analysis techniques were used for structural characterization. A single crystal X-ray diffraction study was performed in order to determine the stereochemistry of the compounds. The optimization geometry of the compounds was obtained by performing density functional theory. However, the global reactivity parameters were estimated from frontier molecular orbitals. The calculated global reactivity parameters showed that the most reactive compoun...

Synthesis and Determination of Acid Dissociation Constants in Dimethyl Sulfoxide–Water Hydroorganic Solvent of 5,5-Diphenylpyrrolidine N-Aroylthiourea Derivatives

Nural, Yahya

Novel 5,5-diphenylpyrrolidine N-aroylthioureas, containing 4-methylbenzoyl, 2- chlorobenzoyl, 2,4-dichlorobenzoyl, and 2-naphthoyl were synthesized, and their structural analyses were performed using 1H Nuclear Magnetic Resonance (NMR), 13C NMR, Fourier transform infrared spectroscopy (FT-IR), mass spectrometry (MS), and high-resolution MS (HRMS) techniques. The acid dissociation constants of the 5,5-diphenylpyrrolidine Naroylthiourea derivative compounds were determined using Hyperquad computer program for data obtained using potentiometric titration method in 25% (v/v) dimethyl sulfoxide–water hydro-organic solvent in the presence of 0.1 molL 1 ionic strength of NaCl and in the acidic medium at 25±0.1 °C, using sodium hydroxide base as a titrant. Two acid dissociation constants ...

Synthesis and Determination of Acid Dissociation Constants of Bis-Acyl Thiourea Derivatives

Efeoglu, Cagla | Tiken, Şit | Nural, Yahya

N,N'-((dodecane-1,12-diylbis(azanediyl))bis(carbonothioyl))bis(4-nitrobenzamide) 5 and N,N'-((dodecane-1,12-diylbis(azanediyl))bis(carbonothioyl))bis(3-nitrobenzamide) 6 as bis acyl thiourea derivatives were synthesized and their molecular structures were characterized using 1H NMR, 13C NMR, COSY, DEPT, HMQC, FT-IR, and HRMS techniques. The acid dissociation constants (pKa) of the bis-acyl thiourea derivatives 5, 6 were determined potentiometrically and spectrophotometrically. The pKa values of products 5, 6 were determined in 50% (v/v) dimethyl sulfoxide–water hydro-organic solvent in the presence of 0.1 molL1 ionic strength of NaCl and in the acidic medium at 25±0.1 °C, and two pKa values were calculated for each compound with the HYPERQUAD computer program using the data obtai...

Determination of Acid Dissociation Constants (pKa) of Bicyclic Thiohydantoin-Pyrrolidine Compounds in 20% Ethanol-Water Hydroorganic Solvent

Nural, Yahya | Dondas, Haci Ali | Belveren, Samet | Gemili, Muge

The acid dissociation constants of potential bioactive fused ring thiohydantoin- pyrrolidine compounds were determined by potentiometric titration in 20% ( v/ v) ethanol- water mixed at 25 +/- 0.1(0) C, at an ionic background of 0.1 mol/ L of NaCl using the HYPERQUAD computer program. Proton affinities of potential donor atoms of the ligands were calculated by AM1 and PM3 semiempiric methods. We found, potentiometrically, three different acid dissociation constants for 1a- f. We suggest that these acid dissociation constants are related to the carboxyl, enol, and amino groups.