Halide Edip Temel

In this study, we have designed ten novel 2‐[1‐[2‐(4‐(substituted phenyl)thiazol‐2‐yl)hydrazono]ethyl]‐4‐nitrophenol ( 2a–2j ) derivatives bearing hydrazone group and thiazole moiety. Target compounds are synthesized via two simple and affordable steps starting from 2‐hydroxy‐5‐nitroacetophenone. Structural confirmation of the resulted compounds performed by APCI‐MS (atmospheric‐pressure chemical ionization mass spectrometer), HRMS (high‐resolution mass spectrometry), ¹ H and ¹³ C NMR (nuclear magnetic resonance) and melting point apparatus. Cyclooxygenase (COX) inhibition of the compounds performed. Anticancer activity of the compounds investigated with apoptosis induction, mitochondrial membrane polarization (ΔΨm), caspase‐3 activity tests. The results of the cytotoxicity assay indicated that compounds 2c , 2e , and 2i exhibited cytotoxic activity comparable to that of cisplatin. Based on the cytotoxicity test results compounds 2c, 2e, 2g, 2h, and 2i selected to performed further investigations. Apoptosis results exhibited that 2c, 2g , and 2i had higher apoptotic induction (early and late apoptosis) rates in A549 cells. Furthermore, 2c showed cisplatin‐like mitochondrial activity at 13.46%. Also, 2c showed notable caspase‐3 enzyme activation on A549 cells. In silico studies indicated that compound 2c interacts with the allosteric cavity of caspase‐3. The findings from the anticancer activity studies suggest that compound 2c may induce cell death through the intrinsic apoptotic pathway.

The quinazoline/quinazolinone ring is known as a unique scaffold, and its derivatives possess a broad biological activity profile, including antibacterial, antifungal, anticonvulsant, anti-inflammatory, anti-HIV, and analgesic activity, primarily focusing on anticancer activity. In this study, the synthesis of 2-[[4-oxo-3-(substituted phenyl)-3,4-dihydro-(substituted quinazolin-2-yl)]thio]-N′-(aryl/heteroaryl methylene)acetohydrazide (4a–4x) derivatives and their potential anticancer activities were investigated on the lung cancer A549 cell line, the breast cancer MCF-7 cell line, and healthy fibroblast L929 cell line. Compounds 4c, 4i, 4m, and 4u were identified as the most cytotoxic and selective molecules on the A549 cell line (IC₅₀: 44.75–78.13 µM), while 4i, 4l, 4m, and 4u were identified as the most cytotoxic and selective molecules on the MCF-7 cell line (IC₅₀: 14.43–29.39 µM). The mechanisms of action of their anticancer activities were examined and studied. It was determined that these compounds induced strong apoptosis and significantly activated caspase-3 activation in both cell types and that they interrupted the cell cycle in the pre-G (sub G0) phase. Compounds 4m and 4u exhibited EGFR inhibition (IC₅₀: 4.80 µM, IC₅₀: 5.40 µM, respectively) at a level similar to the standard drug gefitinib (IC₅₀: 1.86 ± 0.43 µM). Based on the results of the biological activity assays, molecular docking, and molecular dynamics simulation studies, the 4-quinazolinone–acetyl hydrazone scaffold can be considered a promising structural framework with potential anticancer activity. More specifically, the findings of this study indicate that the acetyl moiety may function as an important pharmacophoric group, while the trisubstituted quinazolinone core may represent a favorable structural feature for caspase-3 activation. However, the same structural framework appears to be less favorable for EGFR inhibition, possibly due to steric constraints within the EGFR binding pockets.

In this study, 2‐(heteroaryl thio)‐ N ‐(4‐methylthiazol‐2‐yl)acetamide ( 3a–3i ) derivatives were synthesized, and the anticancer activity of the compounds were investigated on A549 lung cancer and C6 glioma cell lines. Their anti‐inflammatory activities were tested against COX‐1, COX‐2, and LOX enzymes. Compounds 3a and 3c showed high cytotoxic activity against the A549 cell line, while compounds 3b, 3c, and 3f exhibited selective cytotoxicity against C6. Compared to cisplatin, a strong antiproliferative activity was detected against the C6 cell line. Further studies of anticancer treatments revealed that compound 3c significantly induced apoptosis, caspase‐3 activation, and mitochondrial membrane polarization against the A549 cell line. Compound 3c inhibited COX‐1 by 98.11% and 3h by 90.47%, while showing no significant inhibition of COX‐2 or LOX. Compound 3c , a derivative containing 2‐thiazoline, which showed the most potential in terms of both anticancer and anti‐inflammatory activity among all compounds, was subjected to molecular docking studies on Caspase‐3 and COX‐1 enzymes. Compound 3c was found to interact with Ser205, Arg207, and Gly122 of caspase‐3 enzyme via hydrogen bonds, and similarly, due to its hydrophobic property in both caspase‐3 and COX‐1 enzymes, 3c interacts with the hydrophobic regions of amino acids.

Pyridine and thiazolidine ring systems are unique heterocyclic rings since they are present in the structure of various drug/drug‐like molecules and reported in many studies for their distinct biological effects. It is of interest to pharmaceutical chemists because of their chemotherapeutic effect profiles such as antibacterial, antifungal, antiviral, and anticancer; briefly, their cytotoxic effects are very interesting. Because of these cytotoxic activities, in this project, we synthesized chalcone derivatives from the 5 ^th position of the thiazolidin‐4‐one and its linking pyridine by the hydrazone bridge. The antibacterial activities of the resulted compounds on different gram (+) and (−) bacteria and their antifungal activities tested against several invasive fungi. Due to significant fungistatic activity, the inhibitory activity on lanosterol demethylase (LDM, 5TZ1, CYP51A1) and aromatase (3EQM, CYP19A1) enzymes was evaluated, and in silico approaches were used to clarify and explain the binding modes, and then the structure activity relationship (SAR) was reported. Results of the study indicated that designed molecules were successfully obtained with important antifungal activity, and the mechanism of action was clarified.

Lupeol compound is a cyclic triterpene alcohol that is widely found in plants. The compound lupeol has been reported to exhibit antitumor, anti-inflammatory, anxiolytic, neuroprotective and hepatoprotective effects. Recent research shows that lupeol could be a potential medicine for various diseases and also an adjuvant for intractable diseases. Cancer poses a health threat that is increasingly common around the world. Among new cancer cases, lung cancer is one of the most common and deadly cancers worldwide. In this study, the anticancer efficiency of lupeol on human lung adenocarcinoma A549 and glioma C6 cell lines were examined. Various concentrations of lupeol (500, 250, 125, 62.5, 31.25, 15.62, 7.81, 3.90 μM) effectually reduced cell viability in the A549 and C6 cell lines in a dose-dependent manner. These results showed that lupeol had selective anticancer activity against A549 and C6 cell lines.

In an endeavour to identify small molecule COX-1 inhibitors, a colorimetric assay protocol was applied for the in vitro evaluation of COX-1 and 2 inhibitory potential of a series of thiadiazole-benzothiazole hybrids. The most potent and selective COX-1 inhibitor in this series was found as 2-[(5-amino-1,3,4-thiadiazol-2-yl)thio]-N-(6-chlorobenzothiazol-2-yl)acetamide (7) (51.36 ± 3.32% at 100 µM) compared to SC-560 (83.64 ± 3.76% at 1 µM). Compound 7 exerted weaker inhibitory effect on COX-2 (11.05 ± 1.69% at 100 µM). To explore its binding interactions at the active site of human COX-1 (PDB ID: 6Y3C), molecular docking studies were conducted. Compound 7 could establish hydrogen bonds with proper residues thanks to its amide C=O group. In silico studies were employed to shed light on their pharmacokinetic properties. Taken together, compound 7 can be considered as a potential lead compound for the generation of selective COX-1 inhibitors with enhanced efficacy.

Alzheimer’s disease (AD) is basically associated with disturbances of cholinesterase metabolism which result in acetylcholine deficiency. Target of acetylcholinesterase (AChE) inhibitors used in symptomatic therapy of disease is to increase of ACh levels. Consequently, cholinesterase inhibitors were developed to increase acetylcholine is to inhibit AChE and butrylcholinesterase (BuChE). Studies demonstrate the clinical importance of dual inhibitors that inhibit not only the acetylcholinesterase enzyme but also the butyrylcholinesterase enzyme. In recent years, benzimidazoles have attracted particular interest owing to their anticolinesterase activity. In this manner, we have synthesized benzimidazole and morpholine including compounds (2a-i). Final compounds were achieved with the reaction of (benzimidazol-2-yl) methyl morpholine-4-carbodithioate and α-bromoacetophenone derivatives in acetone at room temperature with stirring. Inhibition effects of novel morpholine dithiocarbamates (2a-i) were tested on AChE and BuChE. Compound 2d demonstrated dual inhibitory activity on AChE and BuChE (78±1,56, 70,71±1,53, respectively), with the lowest cytotoxicity to normal cell line.

The medicinal plant Satureja cuneifolia Ten. was widely utilized as spice, tea and traditional medicine. The objective of the current study was to examine the chemical composition and in vitro biological activities (LOX, MMP-1, and MMP-12 enzyme inhibition activity and cytotoxicity on A549 cell line) of Satureja cuneifolia extracts and essential oils. The essential oils of the flowering aerial parts were hydro-distilled at four different distillation times (5, 30, 60, and 180 min) using the Clevenger apparatus. The total essential oil and four fragments were compared in terms of the major component, yield, and distillation time. Volatile compounds of the infusion were extracted by using HS-SPME. Ethanolic extract had the strongest inhibition activity on the LOX enzyme (84.50%), while the essential oils exhibited more cytotoxic activity on the A549 cell line than the extracts. The oils and the infusion were analyzed using GC-MS and the primary chemicals identified by LC-MS/MS.