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Novel halogenated phenoxychalcones 2a-f and their corresponding N-acetylpyrazolines 3a-f were synthesised and evaluated for their anticancer activities against breast cancer cell line (MCF-7) and normal breast cell line (MCF-10a), compared with staurosporine. All compounds showed moderate to good cytotoxic activity when compared to control. Compound 2c was the most active, with IC50 = 1.52 µM and selectivity index = 15.24. Also, chalcone 2f showed significant cytotoxic activity with IC50 = 1.87 µM and selectivity index = 11.03. Compound 2c decreased both total mitogen activated protein kinase (p38a MAPK) and phosphorylated enzyme in MCF-7 cells, suggesting its ability to decrease cell proliferation and survival. It also showed the ability to induce ROS in MCF-7 treated cells. Compound 2c exhibited apoptotic behaviour in MCF-7 cells due to cell accumulation in G2/M phase and elevation in late apoptosis 57.78-fold more than control. Docking studies showed that compounds 2c and 2f interact with p38alpha MAPK active sites. [ABSTRACT FROM AUTHOR]

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Background: Epidemiology continues to be an important research tool in the study of epilepsy and related disorders, providing a better understanding of the frequency, causes, and natural history of the disorder. Objective: To estimate the prevalence of epilepsy in Al-Quseir, Red Sea Governorate, Egypt, and its magnitude of treatment gap. Methods: The study was part of a door-to-door study, including every door, to screen all inhabitants in Al-Quseir (33,818 inhabitants) by three specialists of neurology and 15 female social workers (for demographic data collection) using a standardized screening questionnaire. All suspected cases were subjected to detailed history, clinical examination, and electroencephalogram. Neuroimaging studies and estimation of serum drug level were done in select cases if needed. Results: The study revealed that the lifetime prevalence rate of epilepsy in Al-Quseir is 5.5/1,000, with the highest peak during early childhood, while that of active epilepsy is 3.3/1,000 population. The annual incidence rate is 48/100,000, and the age-specific incidence rate has a U-shaped pattern with two peaks of incidence in early infancy and elderly life. Localizationrelated epilepsy is the most frequently encountered type (58.8%). The treatment gap of epilepsy in Al-Quseir is 83.8%. Conclusion: The lifetime prevalence of epilepsy in Al-Quseir city, Red Sea Governorate, was 5.5/1000. [ABSTRACT FROM AUTHOR]

Background Bell's palsy (BP) is one of the most common causes of acute-onset unilateral facial weakness. Through this study we aimed to estimate the incidence of BP in Al-Quseir City, Red Sea Governorate, Egypt. Patients and methods A project was undertaken to assess the epidemiology of major neurological disorders. A total of 33 285 eligible patients were screened through a door-to-door survey (every door) by three specialists in neurology and 15 social workers. All patients were subjected to detailed history taking and a meticulous neurological examination by means of a specific questionnaire designed for this study. Results Within 1 year, 27 patients were diagnosed with BP. This yielded an incidence rate of 98.9/100 000 population (aged 9 years and older). The incidence was higher in the male population than in the female population (116.4 and 81.2/100 000, respectively). Age-specific incidence of BP showed that its peak was between the ages of 18 and 60 years. About 78% of patients with BP recovered completely within 6 months after onset. There was no significant difference between male and female patients. Conclusion The incidence rate for BP was 98.9/100 000 among those aged 9 years and older. Most affected cases were older than 18 and less than 60 years. [ABSTRACT FROM AUTHOR]

A new series of indolyl 1,2,4-triazole scaffolds was designed, synthesised, and biologically evaluated for their inhibitory activity against both CDK4 and CDK6. The results ranged from 0.049 μM to 3.031 μM on CDK4 and from 0.075 μM to 1.11 μM on CDK6 when compared to staurosporine, with IC 50 values of 1.027 and 0.402 μM, respectively. Moreover, all compounds were tested for their cytotoxicity against two breast cancer cell lines, MCF-7 and MDA-MB-231. All of the synthesised compounds showed promising anti-proliferative activity, with two compounds Vf (IC 50 = 2.91 and 1.914 μM, respectively) and Vg (IC 50 = 0.891 and 3.479 μM, respectively) having potent cytotoxic activity in comparison to the reference staurosporine (IC 50 = 3.144 and 4.385 μM, respectively). Vf and Vg were also found to significantly induce apoptosis to 45.33% and 37.26% (control = 1.91%) where Vf arrested the cell cycle at the S phase while Vg arrested the cycle at the G 0 /G 1 phase. The binding mode and interactions of all compounds were studied and found to mimic those of the FDA approved CDK4/6 inhibitor palbociclib that was used as a reference throughout the study., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

A novel series of pyrimidine-5-carbonitrile derivatives was designed, synthesized, then evaluated for their cytotoxic activity as novel anti-cancer with dual EGFR WT /COX-2 inhibitors. Two compounds 4e and 4f disclosed the highest activity against all NCI60 panel cell lines. They were most potent against Colo 205 (IC 50 = 1.66, and 1.83 μM), Sequentially. The most potent two compounds disturbed cell cycle of Colo-205 cells by blocking the G1 phase, coupled with increased annexin-Vstained cells which indicated the increasing in percentage of apoptosis. In addition, 4e and 4f increase the concentration of caspase-3 by 10, and 8-fold compared to control, respectively. Moreover, the two candidate compounds were screened for cytotoxicity on normal epithelial colon cells; fortunately, they were found to be safe. Molecular docking study displayed that these compounds bound to the active site as EGFR WT /COX-2 inhibitors. Furthermore, 3D pharmacophore mapping disclosed many shared features between the most potent candidates 4e and 4f and the standard EGFR WT /COX-2 inhibitors; erlotinib, and celecoxib, respectively. Finally, the physicochemical parameter was calculated for the most potent novel anticancer candidates and the SwissAdme parameter showed that the newly synthesized compounds have good drug-likeness properties., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Alzheimer's Disease (AD) is a multifactorial incurable neurodegenerative disorder. It is characterized by a decline of cholinergic function in parallel with β-amyloid fibril deposition. Such an imbalance causes severe loss in memory and cognition, leading to behavioral disturbances, depression, and ultimately death. During the last decades, only a few approved drugs were launched onto the market with indications for treating initial and moderate stages of AD. To date, cholinesterase inhibitors (ChEI) are the mainstay line of treatment to ameliorate AD symptoms. Tacrine and Donepezil are the most commonly prescribed anti-dementia drugs, given their potent inhibitory effects. Therefore, many trials have focused on both drugs' structures to synthesize new anti-dementia agents. This paper discusses recent trends of new AD-treating anti-dementia agents focusing on Tacrine and Donepezil analogs and multifunctional hybrid ligands., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)