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Hacettepe University · Faculty of Pharmacy Department of Biochemistry

Using molecular hybridization and bioisosteric replacement approaches, novel agents with potential use for the treatment of Alzheimer’s disease (AD) were developed based on the structure of donepezil. A series of 14 indanone-chalcones bearing ester group were designed, synthesized, and then characterized using variety of methods. All target compoun...

Acetaminophen (APAP) overdosing is the most common cause of drug-induced liver failure. Despite extensive study, N-acetylcysteine is currently the only antidote utilized for treatment. The purpose of this study was to evaluate the effect and mechanisms of phenelzine, an FDA-approved antidepressant, on APAP-induced toxicity in HepG2 cells. The human...

Molecular hybridization and bioisosteric replacement approaches were used to design novel agents with potential use for the treatment of Alzheimer’s disease (AD). Derivatives containing indanone-chalcone core structure bearing ester group were designed and synthesized. In vitro activities of all target compounds against acetylcholinesterase (AChE)...

In this research, a series of coumarin-based scaffolds linked to pyridine derivatives via a flexible aliphatic linkage were synthesized and assessed as multifunctional anti-AD agents. All the compounds showed acceptable acetylcholinesterase (AChE) inhibition activity in the nanomolar range (IC50 = 2–144 nM) and remarkable butyrylcholinesterase (BuC...

Donepezil is the most prescribed drug for mild to moderate Alzheimer's Disease. There is not any alternative drug with this potency yet. New scaffolds bearing benzofurans and amines are being tested for good potency on acetylcholinesterase enzyme to mimic donepezil. In this study, we synthesized 22 novel compounds (2a-b, 3a-t) namely benzofuroyl-ph...

Breast cancer is the most common type of cancer in women. Many genetic and environmental factors play an important role in breast cancer and therefore it is considered as a heterogeneous disease. Nowadays, new treatment approaches are being studied for reasons such as the different treatment responses of the defined subtypes to each other, the deve...

A novel series of coumarin derivatives linked to the N -benzyl triazole group were synthesized and evaluated against 15-lipoxygenase (15-LOX), and acetyl- and butyrylcholinesterase (AChE and BuChE) to find the most potent derivative against Alzheimer’s disease (AD). Most of the compounds showed weak to moderate activity against ChEs. Among the most...

Anti-hormone therapy mediated cognitive decline among cancer patients has been referred to aschemobrain. Current literature indicates that declined estrogen in the brain may be contributing to the genesis of thisphenomenon. Aromatase is a key enzyme that converts C19 steroids to estrogen in the brain, although its involvementin cognitive function h...

Alzheimer’s disease is a disease that causes progressive and irreversible damage to nerve cells, characterized by cognitive and memory impairment. It is the world’s leading cause of dementia and the population of Alzheimer’s patients is growing rapidly. The reasons such as the etiology of the disease not being determined yet, the increase in the pa...

Background Since the binding of estradiol to its receptor promotes breast cancer cell proliferation (in the ER+ tumours), many molecules targeting this protein have been synthesized to counteract the estradiol action. Ferrocene derivatives have proved their efficiency against hormone-dependent breast cancer cells (MCF-7). Objective In this study,...

Bisphenol A (BPA) is an endocrine-disrupting chemical utilized in the manufacture of food packaging, dental materials, medical devices, children's toys, and baby products. Numerous studies have indicated the role of BPA in the etiology of many diseases such as diabetes, cardiovascular diseases, obesity, cancer, and chemotherapeutic resistance. Howe...

Inspired by the structures of donepezil and rivastigmine, a novel series of indanone–carbamate hybrids was synthesized using the pharmacophore hybridization‐based design strategy, and their biological activities toward acetylcholinesterase (AChE) and butyrylcholinesterase were evaluated. Among the synthesized compounds, 4d and 4b showed the highest...

PurposeAlzheimer’s disease (AD) is a multifaceted neurodegenerative disease. To target simultaneously multiple pathological processes involved in AD, natural-origin compounds with unique characteristics are promising scaffolds to develop novel multi-target compounds in the treatment of different neurodegenerative disease, especially AD. In this stu...

New compounds containing indanone and carbamate moieties were designed based on the hybrid pharmacophore approach. The designed compounds were synthesized and fully characterized by using different methods such as IR, Mass, ¹HNMR, ¹³C NMR, and HPTLC. In vitro inhibitory activities of all synthesized compounds were evaluated against acetylcholineste...

The combination of heterocycles offers a new opportunity to create novel multicyclic compounds having improved biological activity. Coumarins are ubiquitous natural heterocycle widely adopted in the design of various biologically active compounds. Fusing different heterocycles with coumarin ring is one of the interesting approaches to generating no...

Carbon-based nanomaterials have received substantial attention as a drug delivery platform for cancer treatment. In the current study, a simple and eco-friendly method was introduced for the preparation of highly fluorinated graphene oxide (FGO), which was subsequently evaluated by standard characterization methods. It was then employed as a carrie...

Neurodegenerative diseases are progressive diseases, affecting many people in today. Due to unknown underlying mechanisms, many studies have been carried out about this subject. in this review, folate's role and mechanism of action on the these diseases were investigated. Folate takes place in the single carbon cycle that is necessary for vital met...

Background Receptor Tyrosine Kinases (RTK) are a main family of cell surface receptors for growth factors, hormones and cytokines which are responsible for cell growth and differentiation and are considered as an important therapeutic target in cancer. Objective The aim of this study was to design, synthesis and biological evaluation of benzimidaz...

The occurrence of amyloid-β (Aβ) and reduced cholinergic tranmission are two major hallmarks of Alzheimer’s disease (AD). Therefore, a series of new 2-phenylbenzo[d]thiazoles substituted with azole/piperazine moieties were designed, synthesized, and evaluated as potential dual inhibitors of Aβ aggregation and cholinesterase (ChE) activities. In vit...

Multi-Target approach is particularly promising way to drug discovery against Alzheimer's disease. In the present study, we synthesized a series of compounds comprising the carbazole backbone linked to the benzyl piperazine, benzyl piperidine, pyridine, quinoline, or isoquinoline moiety through an aliphatic linker and evaluated as cholinesterase in...

Alzheimer's disease (AD) is a neuroinflammatory based pathologic state in which β-amyloid aggregates are major devastating agents. In this study, a series of 2-hydroxyiminoethanones were synthesized and evaluated as anti-inflammatory in carrageenan and formalin tests and inhibitors of β-amyloid aggregation. Compounds 1-10b were synthesized through...

Bisphenol A (BPA, 2,2-bis(4-hydroxyphenyl)propane)polycarbonate is an industrial component frequently used as an additive in the construction of epoxy resin and other non-polymer plastics. In this study cytotoxicity of low dose BPA (0.01 μM-100 μM ) and NO levels in SH-SY5Y cells were assessed together to determine whether there is a correlation be...

A novel series of 2-pyrazoline derivatives was designed, synthesized, and evaluated for cholinesterase (ChE) inhibitory, Aβ anti-aggregating and neuroprotective activities. Among these, 3d, 3e, 3g, and 3h were established as the most potent and selective BChE inhibitors (IC50 = 0.5–3.9 µM), while 3f presented dual inhibitory activity against BChE a...

Two series of novel coumarin derivatives, substituted at 3 and 7 positions with aminoalkoxy groups, are synthesized, characterized, and screened. The effect of amine substituents and the length of cross‐linker are investigated in acetyl‐ and butyrylcholinesterase (AChE and BuChE) inhibition. Target compounds show moderate to potent inhibitory activ...

A novel series of benzylpyridinium-based benzoheterocycles (benzimidazole, benzoxazole or benzothiazole) were designed as potent acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. The title compounds 4a-q were conveniently synthesized via condensation reaction of 1,2-phenylenediamine, 2-aminophenol or 2-aminothiophenol with p...

Bisphenol A (BPA) is an endocrine disruptor chemical, which is commonly used in everyday products. Adverse effects of its exposure are reported even at picomolar doses. Effects of picomolar and nanomolar concentrations of BPA on cytotoxicity, nitric oxide (NO) levels, acetylcholinesterase (AChE) gene expression and activity, and tumor necrosis fact...

New series of triazole-containing 3-phenylcoumarin–lipoic acid conjugates were designed as multi-functional agents for treatment of Alzheimer's disease. The target compounds 4a-o were synthesized via the azide-alkyne cycloaddition reaction and their biological activities were primarily evaluated in terms of neuroprotection against H2O2-induced cell...

A novel series of coumarin-lipoic acid conjugates were synthesized via cycloaddition click reaction to find out new multi-target-directed ligands (MTDLs) for treatment of Alzheimer's disease (AD). All of synthesized compounds were screened for neuroprotective and anti-cholinesterase activities. Based on primary screening, two compounds (5 and 11) w...

A series of 5,6-diaryl-1,2,4-triazine-3-thioacetate derivatives 3a–f, 8a–d and their regioisomer 8e were synthesized. Neuroprotective activity of compounds was assessed against H2O2 and β-amyloid-induced toxicity in PC12 and SH-SY5Y cells respectively. Surprisingly, ethyl 2-(5-(4-chlorophenyl)-6-(4-methoxyphenyl)-3-thioxo-1,2,4-triazin-2(3H)-yl)ace...

This study describes the synthesis, pharmacological evaluation, including acetylcholinesterase (AChE)/butyrylcholinesterase (BChE) inhibition, amyloid beta (Aβ) antiaggregation, and neuroprotective effects, as well as molecular modeling of novel 2-(4-substituted phenyl)-1H-benzimidazole derivatives. These derivatives were synthesized by cyclization...

The present study describes the synthesis, pharmacological evaluation (BChE/AChE inhibition, Aβ antiaggregation, and neuroprotective effects), and molecular modeling studies of novel 2-[4-(4-substitutedpiperazin-1-yl)phenyl]benzimidazole derivatives. The alkyl-substituted derivatives exhibited selective inhibition on BChE with varying efficiency. C...

Bisphenol A (BPA, 2,2-bis (4-hydroxyphenyl) propane) polycarbonate is an industrial component frequently used as an additive in the construction of epoxy resin and other non-polymer plastics. BPA has been described as an endocrine disrupting chemical (EDC) because it has been shown to be estrogenic activity in most studies. The widespread use of BP...

In order to find novel cyclooxygenase (COX)-2 inhibitors for treating inflammatory-based diseases such as Alzheimer's disease (AD), an ethyl carboxylate side chain was added to 5-(4-chlorophenyl)-6-(4-(methylsulfonyl)phenyl)-3-(methylthio)-1,2,4-triazine (lead compound II) to maintain residual inhibition of COX-1 through interacting with Arg120. A...

To find out new agents for treating inflammatory-involved diseases such as Alzheimer's disease (AD), a series of 1,2-diaryl-2-hydroxyiminoethanones containing vicinal diaryl pharmacophore of COX inhibitors were tested by a set of in vitro, in vivo and computational studies. The in vivo study of compounds indicated their prominent anti-inflammatory...

Organophosphates (OPs) are most widely used group of pesticides in the world that are employed in agriculture and militarian sites since the 1940s. These pesticides affect central and peripheral nervous system by inhibiting acetylcholinesterase. OPs have toxic effects on respiratory, gastrointestinal, circulatory, immune, endocrine and nervous syst...

The cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase, are primary targets of organophosphates (OPs). Exposure to OPs can lead to serious cardiovascular complications, respiratory compromise, and death. Current therapy to combat OP poisoning involves an oxime reactivator (2-PAM, obidoxime, TMB4, or HI-6) combined with atropine...

Organophosphates (OPs) exert their toxicity by inhibiting primarily acetylcholinesterase (AChE) and to a lesser extent butyrylcholinesterase (BChE). Binary mixtures of mammalian AChE and oximes of varying structure have been recently considered for treatment of OP poisoning as catalytic bioscavengers. In this study wild type human AChE and human AC...

The effects of three cationic triarylmethane dyes--pararosaniline (PR), malachite green (MG), methyl green (MetG)--on electric eel AChE (eAChE) activity were tested at 25 degrees C, in 100 mM MOPS buffer (pH 8) containing 0.125 mM 5-5-dithio-bis(2-nitrobenzoic acid), 20-120 microM acetylthiocholine and 0-20 microM dye. All three dyes caused reversi...

Two cationic phenoxazine dyes, meldola blue (MB) and nile blue (NB), and the structurally related phenothiazine, methylene blue (MethB), were found to act as complex inhibitors of human plasma cholinesterase (butyrylcholinesterase, BChE). Studied at 25 degrees C, in 100mM MOPS buffer (pH 8.0), with butyrylthiocholine as substrate, the kinetic patte...

The inhibitory effects of the cationic triarylmethane (TAM+) dyes, pararosaniline (PR+), malachite green (MG+), and methyl green (MeG+) on human plasma cholinesterase (BChE) were studied at 25 degrees C in 100 mM Mops, pH 8.0, with butyrylthiocholine as substrate. PR+ and MG+ caused linear mixed inhibition of enzyme activity. The respective inhibit...