Synthesis of novel immunomodulatory 1,4-disubstituted bis-1,2,3-triazoles by using click chemistry and their intracellular mechanism of action
Nural, Yahya | Acar, Irem | Yetkin, Derya | Efeoglu, Cagla | Ayaz, Furkan
In this study, six new 1,4-disubstituted bis-1,2,3-triazole compounds, N,N '-(1,2-phenylene)bis(2-(4-R-1H-1,2,3triazol-1-yl)acetamide), were synthesized with high yield (88-96 %) by using click chemistry and their molecular structures were characterized by using NMR, FT-IR, HRMS and elemental analysis techniques. Previous studies suggest anti-inflammatory and analgesic activities for different 1,2,3-triazole derivatives and in the light of those studies we aimed to examine these novel derivatives immunomodulatory activities on the mammalian macrophages. Pro-inflammatory cytokines (TNF, IL6, GMCSF and IL12p40) secretion levels were tested in the presence of bis-1,2,3-triazole compounds when the macrophages were activated with LPS. These new derivatives were able to suppress the product...
Novel highly functionalized 1,4-naphthoquinone 2-iminothiazole hybrids: Synthesis, photophysical properties, crystal structure, DFT studies, and anti(myco)bacterial/antifungal activity
Gemili, Muge | Nural, Yahya | Ülger, Mahmut | Erat, Selma
In this paper, a series of novel highly functionalized 1,4-naphthoquinone 2-iminothiazole hybrids were synthesized via a cyclization reaction of 2,3-diaminonaphthalene-1,4-dione N-aroylthioureas and alpha-bromoketones in good to excellent yields (74-94%). The stereochemistry of one of the 1,4-naphthoquinone 2-iminothiazole products was characterized by single crystal X-ray diffraction technique. Photophysical properties of the compounds in DMSO, HAc and THF were determined by using UV-vis spectroscopy. The ground state geometries and the absorption spectra of the compounds were also determined using Density Functional Theory (DFT) and time-dependent DFT (TD-DFT) at B3LYP/631 + g(d,p) level of theory. The computed results are consistent with experimental values. An antimicrobial screening w...
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...
New bis- and tetrakis-1,2,3-triazole derivatives: Synthesis, DNA cleavage, molecular docking, antimicrobial, antioxidant activity and acid dissociation constants
Nural, Yahya | Özdemir, Sadin | Yalçın, Mustafa Serkan | Demir, Bünyamin
In this study, a series of bis– and tetrakis–1,2,3–triazole derivatives were synthesized using copper-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry in 73–95% yield. The bis– and tetrakis–1,2,3–triazoles exhibited significant DNA cleavage activity while the tetrakis–1,2,3–triazole analog 6g completely degraded the plasmid DNA. Molecular docking simulations suggest that compound 6g acts as minor groove binder of DNA by binding through several noncovalent interactions with base pairs. All bis- and tetrakis–1,2,3-triazole derivatives were screened for antibacterial activity against E. coli, B. cereus, S. aureus, P. aeruginosa, E. hirae, L. pneumophila subsp. pneumophila strains and antifungal activity against microfungus C. albicans and C. tropicalis strains. Compound 4d exhibit...
Novel urea-thiourea hybrids bearing 1,4-naphthoquinone moiety: Anti-inflammatory activity on mammalian macrophages by regulating intracellular PI3K pathway, and molecular docking study
Efeoglu, Cagla | Yetkin, Derya | Nural, Yahya | Ayaz, Furkan
In this study, four novel urea-thiourea hybrids bearing 1,4-naphthoquinone moiety were synthesized by the reaction of 2,3-diaminonaphthalene-1,4-dione and various isothiocyanate derivatives in 75-88% yield, and their molecular structures were characterized by using H-1/C-13 NMR, FT-IR and HRMS techniques. Urea-thiourea hybrids have been known for their anti-inflammatory activities. Therefore, in our study, we aimed to decipher their biological activities on mammalian macrophages. Macrophages were stimulated by LPS and pro-inflammatory TNF, IL6, GMCSF and IL12p40 cytokine production levels were measured in the presence of these derivatives by ELISA. Our results suggest that these derivatives on stimulated mammalian macrophages had anti-inflammatory activities. In order to examine their intr...
Synthesis of novel acylthioureas bearing naphthoquinone moiety as dual sensor for high-performance naked-eye colorimetric and fluorescence detection of CN− and F− ions and its application in water and food samples
Nural, Yahya | Karasu, Elize | Efeoglu, Cagla
In this study, six new acylthiourea, bearing naphthoquinone moiety, sensors were synthesized in high yield (88-96%) and characterized using H-1/C-13 NMR, FT-IR and HRMS techniques. All synthesized sensors (4a-f) showed shifts in absorbance and colorimetric changes by CN-, F-, AcO-, and H2PO4-. However, 4e showed a chromogenic different sensitivity response to CN- and F- against competing anions such as AcO- and H2PO4- in DMSO. Furthermore, CN- added 4e showed an increase at the emission intensity and intensive fluorimetric color change was observed in UV-light (lambda ex. 365 nm). All sensors showed chromogenic selectivity towards CN- in aqueous solutions (in DMSO/H2O: 1:1, v/v). Interaction mechanisms between 4e and CN- and F- anions were investigated by experimental studies using various...
Novel fluorescent sensors based on coumarin-hydrazide-hydrazone hybrid for the detection of CN-, Co2+ and Ni2+ ions: DFT and bioimaging in living cells
Nural, Yahya
Novel coumarin-hydrazide-hydrazone hybrids, (E)-7-(diethylamino)-N '-(2-hydroxy-3-methoxybenzylidene)-2oxo-2H-chromene-3-carbohydrazide (1) and (E)-7-(diethylamino)-N '-(4-(diethylamino)-2-hydroxybenzylidene)2-oxo-2H-chromene-3-carbohydrazide (2), were synthesized and investigated their chemosensor properties. The sensors showed recognition properties of CN-, Co2+, and Ni2+ ions. After interaction with the cyanide anion, the coumarin-hydrazide-hydrazone sensors exhibited a color change visible to the naked eye, from yellow to colorless under daylight and from blue to green under UV light. The sensors exhibited a significant fluorescent enhancement response to the cyanide anion by the intramolecular charge transfer (ICT) mechanism. Furthermore, the recognition of cations was obser...
New bis-and tetrakis-1, 2, 3-triazole derivatives: Synthesis, DNA cleavage, molecular docking, antimicrobial, antioxidant activity and acid dissociation constants
Nural, Yahya | Ozdemir, Sadin | Yalcin, Mustafa Serkan | Demir, Bunyamin
In this study, a series of bis- and tetrakis-1,2,3-triazole derivatives were synthesized using copper-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry in 73-95% yield. The bis- and tetrakis-1,2,3-triazoles exhibited significant DNA cleavage activity while the tetrakis-1,2,3-triazole analog 6g completely degraded the plasmid DNA. Molecular docking simulations suggest that compound 6g acts as minor groove binder of DNA by binding through several noncovalent interactions with base pairs. All bis- and tetrakis-1,2,3-triazole derivatives were screened for antibacterial activity against E. coli, B. cereus, S. aureus, P. aeruginosa, E. hirae, L. pneumophila subsp. pneumophila strains and antifungal activity against microfungus C. albicans and C. tropicalis strains. Compound 4d exhibit...
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...
Novel urea-thiourea hybrids bearing 1,4-naphthoquinone moiety: Anti-inflammatory activity on mammalian macrophages by regulating intracellular PI3K pathway, and molecular docking study
Efeoglu, Cagla | Yetkin, Derya | Nural, Yahya | Ayaz, Furkan
In this study, four novel urea-thiourea hybrids bearing 1,4-naphthoquinone moiety were synthesized by the reaction of 2,3-diaminonaphthalene-1,4-dione and various isothiocyanate derivatives in 75-88% yield, and their molecular structures were characterized by using H-1/C-13 NMR, FT-IR and HRMS techniques. Urea-thiourea hybrids have been known for their anti-inflammatory activities. Therefore, in our study, we aimed to decipher their biological activities on mammalian macrophages. Macrophages were stimulated by LPS and pro-inflammatory TNF, IL6, GMCSF and IL12p40 cytokine production levels were measured in the presence of these derivatives by ELISA. Our results suggest that these derivatives on stimulated mammalian macrophages had anti-inflammatory activities. In order to examine their intr...