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...

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...

Synthesis of Ni(II), Pd(II) and Cu(II) metal complexes of novel highly functionalized aroylaminocarbo-N-thioyl pyrrolidines and their activity against fungi and yeast

Nural, Yahya | Dondas, Haci Ali | Serin, Mehmet Sami | Ince, Tuncay

A series of Ni(II), Pd(II) and Cu(II) metal complexes of highly functionalized aroylaminocarbo-N-thioyl pyrrolidines were prepared and characterized by microanalysis, spectroscopic methods, magnetic susceptibility measurements and single crystal X-ray diffraction studies. The antifungal activity of the metal complexes against the yeast Saccharomyces cerevisae and against the fungus Penicillium digitatum was studied.

1,4-Naphthoquinone thiazole urea hybrids bearing morpholine/piperazine: synthesis, crystal structure, aldose reductase and α-glycosidase enzyme inhibition, molecular docking, and electrochemical interaction with dsDNA

Efeoglu, Cagla | Nural, Yahya

In this study, new 1,4-naphthoquinone thiazole urea hybrids bearing morpholine (3a-d) or piperazine (3e-h) moiety were synthesized in 76-89 % yields and characterized by 1H NMR, 13C NMR, FT-IR, HRMS, and elemental analysis. The stereochemistry of 3d was determined by single crystal x-ray diffraction study. We evaluated the inhibitory potential of these compounds 3a-h on aldose reductase (ALR2) and alpha-glycosidase enzyme (alpha-GLY) activity. Our results indicate that these compounds substantially inhibit ALR2 at micromolar doses, with inhibition constants (KIs) between 0.79 and 2.20 mu M and inhibit alpha-GLY KI between 0.67 and 2.82 mu M. Molecular docking simulations were utilized to elucidate inhibitory effects and establish structure-activity relationships for the synthesized compoun...

Assessment of eutrophication in a Ramsar site (Akyatan Lagoon) in the Northeastern Mediterranean Sea

NAHİT SONER BÖREKÇİ | İSMAİL AKÇAY | ÖZGÜR ÖZBAY | MEHMET TAHİR ALP

Coastal lagoons are transitional zones between riverine and marine systems where nutrients and contaminants often accumulate in these aquatic environments. In the present study, physical and biochemical data were obtained from the five stations between January and December 2022 for the determination of trophic status in the Akyatan Lagoon. The study results indicated the values of physical and eutrophication-related parameters displayed spatial and temporal variability. The trophic status of Akyatan Lagoon was determined by using two multi-metric classification tools as Trophic index (TRIX) and the Trophic status index (TSI). The calculated TRIX values ranged from 4.88 to 7.90 whilst the TSI values varied between 50.0 and 77.4. The strong and positive correlations between the TRIX and TSI...

Diastereoselective synthesis of 6-functionalized 4-aryl-1,3-oxazinan-2-ones and their application in the synthesis of 3-aryl-1,3-aminoalcohols and 6-arylpiperidine-2,4-diones

Nural, Yahya | Dondas, Haci Ali

Halocyclocarbamation of benzyl N-(1-phenyl-3-butenyl)carbamates afforded 6-functionalized 4-aryl-1,3-oxazinan-2-ones with moderate to excellent diastereoselectivity depending on the N-substituent. Importantly, in contrast to reported cyclocarbamations of homoallylic carbamates, which are generally trans-diastereoselective, cyclization of N-unsubstituted Cbz-protected homoallylamines led to cis-1,3-oxazinan-2-ones, predominantly. The use of N-benzylated and in situ prepared N-silylated derivatives resulted however in trans-selectivity. Transition states are proposed to explain the stereochemical influence of the N-substituent on the cyclocarbamations. The functionalized 1,3-oxazinan-2-ones could be further elaborated towards biologically or synthetically important 6-arylpiperidine-2,4-dione...

Evaluation of hard tissue characteristics and calcifications in pulp tissue of hypomineralized permanent molars using micro-computed tomography

Objectives To determine and compare pulp volume, dentin mineral density, presence of microcracks, pulp stones, and accessory canals, as well as their localizations in root regions for hypomineralized and healthy teeth. Design This study included 60 extracted permanent molar teeth, categorized into hypomineralized and healthy groups (n = 30 each). The hypomineralized group comprised molar teeth with limited white, yellow, or brown opacities, post-eruptive breakdown, or extensive restoration or crown damage. The healthy group included caries-free molar teeth without these characteristics. Using 3D micro-computed tomography images pulp volume, dentin mineral density, and the presence and locations of microcracks, pulp stones, and accessory canals were determined for each group. Statistical...