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In this work, dendritic, water‐soluble, and nonaggregated axially substituted silicon phthalocyanines (EA‐TD‐Si and EA‐TD‐SiQ) were synthesized and characterized. Then, the supercoiled pBR322 plasmid DNA damage properties of EA‐TD‐Si and EA‐TD‐SiQ were examined using agarose gel electrophoresis without light irradiation. In addition, the cytotoxicity and phototoxicity of EA‐TD‐Si and EA‐TD‐SiQ on human endometrium adenocarcinoma (HEC‐1B) cells were investigated using an MTT assay. The results indicated that EA‐TD‐SiQ had high photodamage properties via singlet oxygen depending on the light dose, while EA‐TD‐Si did not show any DNA damage without light. In addition, EA‐TD‐SiQ had higher phototoxic effects than EA‐TD‐Si on HEC‐1B cells according to the MTT assay. These results revealed the potential of EA‐TD‐SiQ to be used as a PDT agent in endometrial cancer. [ABSTRACT FROM AUTHOR]

Alzheimer's disease, is one of the irreversible neurodegenerative disorders among older people, causes behavior, memory, and thinking problems. This study aim is to synthesize of 4‐({8‐[3‐(dimethylamino)phenoxy]octyl}oxy)phthalonitrile, zinc(II) phthalocyanine and its water soluble derivative containing ({8‐[3‐(dimethylamino)phenoxy]octyl}oxy) substituents at the peripheral positions first time. To determine the potential of water soluble silicon(IV) and zinc(II) phthalocyanines for use in AD, spectrophotometric assays were performed to determine their acetylcholinesterase/butyrylcholinesterase inhibitory effects. In addition, their DNA nuclease properties were evaluated by agarose gel electrophoresis. The results showed that the compounds inhibited acetylcholinesterase/butyrylcholinesterase. They did not damage pBR322 plasmid DNA depending on time and concentration. As a result of the experiments, it is revealed that the compounds may be the potential for use as cholinesterase inhibitors, which is a promising approach for the treatment of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

In this study, magnesium (II) phthalocyanines (2a, 3a) and their water‐soluble derivatives (2b, 3b) were synthesized via multistep reactions. The structures of these phthalocyanines were identified by FT‐IR, NMR, MALDI‐TOF, and UV–Vis spectroscopy. The ct‐DNA binding (UV–Vis absorption, competitive EB binding, and agarose electrophoresis studies) and supercoiled plasmid DNA nuclease properties (hydrolytic, photonuclease, oxidative nuclease, and photooxidative nuclease) of the water‐soluble compounds were investigated using different methods. The DNA binding constant (Kb) values of 2b and 3b were calculated as 8.45 ± (0.25) × 104 and 7.71 ± (0.13) × 104 M−1 at 25°C, respectively. The results showed that 2b had a stronger ct‐DNA binding effect than 3b according to Kb and r values. The DNA nuclease studies claimed that both compounds indicated photonuclease activity on plasmid DNA depending on the light dose. Additionally, 2b had a higher photonuclease capacity than 3b. All of these results showed that 2b had promising potential as a photosensitizer agent for photodynamic therapy. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), one of the main causes of dementia, is a neurodegenerative disorder. Cholinesterase inhibitors are used in the treatment of AD, but prolonged use of these drugs can lead to serious side effects. Drug repurposing is an approach that aims to reveal the effectiveness of drugs in different diseases beyond their clinical uses. In this work, we investigated in vitro and in silico inhibitory effects of 11 different drugs on cholinesterases. The results showed that trimebutine, theophylline, and levamisole had the highest acetylcholinesterase inhibitory actions among the tested drugs, and these drugs inhibited by 68.70 ± 0.46, 53.25 ± 3.40, and 44.03 ± 1.20%, respectively at 1000 µM. In addition, these drugs are bound to acetylcholinesterase via competitive manner. Molecular modeling predicted good fitness in acetylcholinesterase active site for these drugs and possible central nervous system action for trimebutine. All of these results demonstrated that trimebutine was determined to be the drug with the highest potential for use in AD. [ABSTRACT FROM AUTHOR]

Azoles, which have been used for antifungal chemotherapy for decades, have recently been of interest for their efficacy against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). There is little known about the potential of azoles against BChE, however there is none regarding their inhibitory effects against mutants of BChE. In the current study, an azole library of 1‐aryl‐2‐(1H‐imidazol‐1‐yl)ethanol/ethanone oxime esters were tested against AChE and BChE, which yielded derivates more potent than the positive control, galantamine, against both isoforms. Kinetic analyses were performed for wildtype and mutant (A328F and A328Y) inhibition for the two most potent BChE inhibitors, pivalic and 3‐bezoylpropanoic acid esters of 2‐(1H‐imidazol‐1‐yl)‐1‐(2‐naphthyl)ethanol, which were found to have great affinity to the wildtype and mutant BChE types with Ki values as low as 0.173 ± 0.012 µM. The compounds were identified to show linear competitive or mixed type inhibition. Molecular modeling confirmed these kinetic data and provided further insights regarding molecular basis of BChE inhibition by the active derivatives. Thus, current study suggests new azole derivatives with promising cholinesterase inhibitory effects and reveals the first set of information to promote our understanding for the inhibitory behavior of this class against the mutant BChE forms. [ABSTRACT FROM AUTHOR]

In this work, 3‐({6‐[3‐(dimethylamino)phenoxy]hexyl}oxy)phthalonitrile (2) and the target zinc (II) phthalocyanine (3) and its ammonium derivative (3a) are synthesized, and the phototoxic effects of 3a were examined using different methods on A549 lung cancer cells. Then, the toll‐like receptor (TLR) signaling pathway was examined to determine the cell death mechanism in the A549 cancer cells. The results showed that 3a did not have noticeable cytotoxic actions on A549 cells at used concentrations. However, the compound markedly reduced the cell viability when irradiated by the red light for 5 and 15 min (LumaCare/LC‐122A/LC2020‐09‐784, Prob: LUM L [700 nm CL] [15 mW cm−2]). Additionally, Annexin V/PI staining suggested that the cells were induced apoptosis in the presence of 3a (1 μM) when irradiated with red light for 15 min. Furthermore, the expression of TLR2, TLR4, and caspase‐3 significantly increased and phospho‐nuclear factor kappa B/total nuclear factor kappa B decreased compared with that of control group (p < 0.05). These results provide strong evidence that 3a is able to induce A549 cell death in a dose and a red‐light irradiation time‐dependent manner via apoptosis. Therefore, 3a might be an effective photodynamic therapy candidate for lung cancer treatment. [ABSTRACT FROM AUTHOR]