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Background and purpose: Alzheimer's disease is the most common form of dementia and the sixth most common cause of death in the US according to the Alzheimer's Association. As regards, to date, no effective treatments are available because of the multifactorial nature of the disease, therefore, a large body of recent research has been allocated to the design and development of multi-target-directed ligands that can become effective drug candidates. Experimental approach: A novel series of benzamide derivatives (5a-5l) containing piperidine core were synthesized in the current work. After identification of the chemical structures of the members of this series using 1 H NMR, IR, and MS spectra, their anti-acetylcholinesterase activity was assessed by the Ellman's test. Docking studies were also performed to investigate the binding mode and determine the interacting amino acids with the corresponding ligands. Finally, the pharmacokinetic (ADME parameters) of the most potent derivative (5d) was predicted and compared with donepezil. Findings/Results: Compound 5d possessing the fluorine atom substitution at position ortho was the most active compound in these series (IC50 = 13 ± 2.1 nM). This compound demonstrated superior activity than the reference drug donepezil (IC50 = 0.6 ± 0.05 µM). Molecular docking showed a significant hydrogen bonding of the carbonyl group of compounds 5d with tyrosine 121 into the active site of acetylcholinesterase. Fortunately, this compound showed better promising ADME properties than donepezil. Conclusion and implication: The benzamide derivatives introduced in this paper could be proposed as potential anti-acetylcholinesterase. [ABSTRACT FROM AUTHOR]

Background and purpose: Malaria and cancer are two major health issues affecting millions of lives annually. Maltol complexes and derivatives have been extensively investigated as chemotherapeutic and antimalarial activities. In this study, the design, synthesis, biological activities, and docking study of a novel series of pyridinones derivatives were reported. Experimental approach: The chemical structures of synthesized compounds were approved by FTIR, 1HNMR, 13CNMR, and mass spectroscopies. The antimalarial activity was evaluated through β-hematin inhibition assay and the cytotoxicity activities were evaluated against PC12 and fibroblast cell lines via MTT and cell uptake assays. To theoretically investigate the ability of compounds to inhibit hemozoin formation, the synthesized compounds were docked in a heme sheet to explore their binding mode and possible interactions. Findings/Results: β-Hematin inhibition assay showed acceptable activity for 7f, 7c, and 7d compounds and the molecular docking study showed 7h and 7f had effective interactions with the heme sheet. The cytotoxic study revealed compound 4b (IC50 = 18 μM) was significantly more active against PC12 cells than docetaxel (IC50 = 280 μM). The observations of cell uptake images were also shown both cell penetration and monitoring potential of synthesized compounds. Conclusion and implications: The compounds showed a moderate ability to inhibition of heme polymerization and also good interaction with heme through molecular docking was observed. Additionally, some of them have a good cytotoxic effect on the study2 cell line. So further study on these compounds can lead to compounds that can be considered as anti-malarial and/or anticancer agents. [ABSTRACT FROM AUTHOR]

Objective(s): Cancer is the second important reason for death worldwide. In spite of advances in cancer treatment, however, survival of patients stays weak. Therefore, there is a critical need for advancement of new anticancer drugs. Regarding the hopeful biological activity of phthalimide derivatives, in this study, synthesis, cytotoxicity, and pro‐apoptosis activity of eleven derivatives of thiazole bearing phthalimide structure were evaluated. Materials and Methods: First, target derivatives were synthesized. All synthesized compounds were characterized by spectroscopic methods. Cytotoxicity and pro‐apoptosis activity of the synthesized compounds were evaluated in MDA-MB-468, PC-12, and MCF-7 cancer cell lines by MTT assay, caspase-3 activity, and TUNEL assay. Finally, expression of BAX, BCL-2, and FAS (as markers of apoptosis) was assessed by the RT-PCR procedure. Results: Among the eleven compounds, 5b (IC50 = 0.2±0.01 μM) was found to be the most potent derivative against MCF-7 cells. Also, Compound 5k and 5g showed strong cytotoxic activity against MDA-MB-468 and PC-12 cells with IC50 value of 0.6±0.04 μM and 0.43±0.06 μM, respectively. DNA fragmentation and activity of caspase-3 data suggest that cytotoxic activity of the compounds on cancer cells might be related to apoptosis. Also, RT-PCR of apoptosis markers indicated that these compounds induce apoptosis through the intrinsic pathway. Conclusion: Our findings suggest that para chloro derivative (5c) may be a promising agent for treatment of cancer cells by the targeted intrinsic pathway of apoptosis and could be used as a drug candidate for in vivo assessment in the treatment of cancer. [ABSTRACT FROM AUTHOR]

Coordination compound (dmapH)2[Sn(pydc)3]·2H2O (where pydc is pyridine-2,6-dicarboxylate and dmapH is 4-dimethylaminopyridine) was prepared from the reaction between the proton-transfer compound, [dmapH]2[pydc2−] and SnCl4·5H2O metal salt. The structure was fully characterized by single-crystal X-ray diffraction and distorted tricapped triangular prism geometry was realized for it. The thermal behavior of the complex was investigated by TGA-DTA analyses. Then, inhibitory effect of both the complex and its ligand was tested, using oxaliplatin as a standard, under MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) method, against U251 (a human glioblastoma), H1299 (a human non-small cell lung carcinoma), βTC (a mouse beta pancreatic), A431 (an epidermoid carcinoma) and HFF (a human foreskin fibroblast) cell lines. Potent and selective anti-proliferative effect of the complex (IC50 = 1 μM, MAE = 65.32%) and also intense decrease of mitochondrial membrane potential (MMP) was exhibited on A431 cells. Evaluation of reactive oxygen species (ROS) in cited cells confirmed that apoptotic pathway may be a possible mode for the death of cells. In order to evaluate the cellular internalization potential of the complex, A431 cells were incubated with it at IC50 concentration. The recorded fluorescent images confirmed successful penetration of the complex. [ABSTRACT FROM AUTHOR]

Due to resistance of some epileptic patients to the current medications and the general incidence of severe side effects of these drugs, development and discovery of novel antiepileptic drugs is crucial. Isatin-based derivatives are promising compounds as antiepileptic agents. In this study a new series of isatin-containing derivatives were synthesized via the imine formation between isatin and p-aminobenzoic acid. Subsequently, the obtained acidic compound was utilized to prepare the final amidic derivatives (4a-4l) through the reaction with various aniline derivatives. Then, their anti-seizure activity was investigated using maximal electroshock seizure (MES) as well as pentylenetetrazole (PTZ) models in mice. Neurotoxicity of target compounds was also determined by rotarod test. Tested isatin-based derivatives exhibited a favorable protection in both MES and PTZ procedures with high safety levels in neurotoxicity test. The introduced derivatives have demonstrated remarkable activity in mice and could be suggested as potential anticonvulsant lead compounds. All methoxylated derivatives (4j, 4k, 4l) showed a significant anti-seizure activity in MES model. Compounds 4j (2-OCH3) and 4l (4-OCH3) also demonstrated a potent anti-seizure activity against PTZ. Compound 4k (m-OCH3) did not induce protection towards PTZ-induced convulsion. [ABSTRACT FROM AUTHOR]