Inhibitory potential of nitrogen,oxygen and sulfur containing heterocyclic scaffolds against acetylcholinesterase and butyrylcholinesterase

Heterocycles are the key structures in organic chemistry owing to their immense applications in the biological, chemical, and pharmaceutical fields. Heterocyclic compounds perform various noteworthy functions in nature, medication, innovation etc. Most frequently, pure nitrogen heterocycles or various positional combinations of nitrogen, oxygen, and sulfur atoms in five or six-membered rings can be found. Inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes is a popular strategy for the management of numerous mental diseases. In this context, cholinesterase inhibitors are utilized to relieve the symptoms of neurological illnesses like dementia and Alzheimer''s disease (AD). The present review focuses on various heterocyclic scaffolds and their role in designing and developing new potential AChE and BChE inhibitors to treat AD. Moreover, a detailed structure–activity relationship (SAR) has been established for the future discovery of novel drugs for the treatment of AD. Most of the heterocyclic motifs have been used in the design of new potent cholinesterase inhibitors. In this regard, this review is an endeavor to summarize the biological and chemical studies over the past decade (2010–2022) describing the pursuit of new N, O and S containing heterocycles which can offer a rich supply of promising AChE and BChE inhibitory activities.

The present review focuses on various heterocyclic scaffolds and their role in designing and developing new potential AChE and BChE inhibitors to treat AD.     

Thymoquinone: a promising antidiabetic agent

The antidiabetic property of Nigella sativa seeds oil are attributable to the presence of Thymoquinone (TQ) which is considered as a major phytochemical component of the seeds volatile oil. The aim of this review is to highlight the potential of thymoquinone as an antidiabetic agent and the latest reported research investigations regarding the molecular mechanism of its hypoglycemic effect. For researchers involved in the field of antidiabetic therapy, clinical testing of the efficacy of TQ in human diabetic patients could provide plenty of opportunities for further research.     

Selected Dietary Nutrients and the Prevalence of Metabolic Syndrome in Adult Males and Females in Saudi Arabia: A Pilot Study

During the last decade, the rapid economic development in Saudi Arabia resulted in an unbalanced dietary intake pattern within the general population. Consequently, metabolic syndrome was also documented to be highly prevalent in the Middle-East region. We aimed to examine the relationship between selected dietary nutrient intakes and the prevalence of metabolic syndrome in the general adult population of Riyadh, Saudi Arabia. In this cross-sectional study, 185 adult Saudis aged 19 to 60 years (87 males and 98 females (mean age 35.6 ± 13.2 and 37.6 ± 11.7 years, respectively)) were included. The criteria for metabolic syndrome were based on the International Diabetes Foundation (IDF) criteria, and the dietary food intake was assessed by two 24-h dietary recall methods. The odd ratios (ORs) of metabolic syndrome risk across quartiles of selected dietary nutrients were significantly lower for carbohydrates and proteins, as well as for vitamins A, C, E and K, calcium, zinc and magnesium (p < 0.05 for all) in the female group with metabolic syndrome than those without. The pattern of daily dietary intake of selected nutrients among the general population of Saudi Arabia raises concern, and this dietary imbalance could increase the risk of metabolic syndrome, particularly in adult Saudi females.     

Choosing drugs for the treatment of diabetic neuropathy

Introduction: Diabetic sensorimotor polyneuropathy (DSP) affects 50% of diabetes patients and is painful in about 26%. Although disease-modifying therapies are not available for DSP, symptomatic treatments for painful diabetic neuropathy (PDN) are effective.

Areas covered: We performed a MEDLINE search on PubMed using the search terms: treatment diabetic neuropathy and treatment PDN. This review outlines the problem posed by DSP, the clinical presentation and the characterization of PDN. A discussion of disease-modifying interventions, including the benefits of strict glycemic control, is followed by a focus on interventions for PDN including antidepressants, anticonvulsants and other treatments.

Expert opinion: Disease modification in DSP remains an unmet need in clinical medicine affecting a large percentage of the population with concomitant healthcare costs. Strict glycemic control and attention to potential risk factors such as hypertension, hyperlipidemia and obesity may minimize DSP. Many patients benefit from treatment of their painful symptoms with anticonvulsants or antidepressants, but all are associated with significant side effects that limit their usefulness. There is a need for treatments of PDN with fewer side effects and more effective pain relief.     

Long-stay patients in pediatric intensive care units: Five-years, 2-points,cross-sectional study

Objectives:To explore the changing patterns of long-stay patients (LSP) to improve the utilization of pediatric intensive care units (PICUs) resources.Methods:This is a 2-points cross-sectional study (5 years apart; 2014-2019) conducted among PICUs and SCICUs in Riyadh, Saudi Arabia. Children who have stayed in PICU for more than 21 days were included.Results:Out of the 11 units approached, 10 (90%) agreed to participate. The prevalence of LSP in all these hospitals decreased from 32% (48/150) in 2014 to 23.4% (35/149) in 2019. The length of stay ranged from 22 days to 13.5 years. The majority of LSP had a neuromuscular or cardiac disease and were admitted with respiratory compromise. Ventilator-associated pneumonia was the most prevalent complication (37.5%). The most commonly used resources were mechanical ventilation (93.8%), antibiotics (60.4%), and blood-products transfusions (35.4%). The most common reason for the extended stay was medical reasons (51.1%), followed by a lack of family resources (26.5%) or lack of referral to long-term care facilities (22.4%).Conclusion:A long-stay is associated with significant critical care bed occupancy, complications, and utilization of resources that could be otherwise utilized as surge capacity for critical care services. Decreasing occupancy in this multicenter study deserves further engagement of the healthcare leaders and families to maximize the utilization of resources.     

Oncology research in Saudi Arabia over a 10-year period: A synopsis

Objectives:To assess the quality and quantity of Saudi publications in oncology over a 10-year period.Methods:A systematic PubMed search was conducted between January 2008 and December 2017 to retrieve all Saudi oncology publications. Data about the articles was collected. The level of evidence (LOE) was independently assessed by 2 authors. Two 5-year periods (2008-2012 and 2013-2017) were compared using the relevant parameters. Clinicaltrials.gov was also searched for all oncology trials registered in Saudi Arabia.Results:A total of 839 publications met our inclusion criteria. The most common type of research was case series, totaling 32% of all publications. Clinical trials formed less than 2% of the total. The LOE was I, II, III, and IV in 0.3%, 2.1%, 58.4%, and 39.3% of the included publications, respectively. The LOE was the same in the 2 periods. There were more publications in international journals (p=0.004), more international collaborations (p=0.001), and higher journal impact factors (p=0.037) in 2013-2017 than in 2008-2012. Only 76 registered clinical trials were found in the Clinicaltrials.gov registry.Conclusion:Despite an increase in the number of Saudi publications in the field of oncology over time, the LOE did not change. There were, however, some improvements in the international collaboration and journal impact factor, as well as an increase in the number of studies published in international journals. These observations call for a national strategy to improve oncology research in Saudi Arabia.     

Social Impact of Dialysis on Children and Their Families

Objectives

To evaluate the social consequences of dialysis on children and their parents.

Methods

From January through June 2012 short structured interviews with parents or caregivers of children on peritoneal dialysis (PD) or hemodialysis (HD) who were followed up at King Abdulaziz University Hospital, King Faisal Specialty Hospital and Research Center, or the Kidney Center at King Fahad Hospital were conducted. Data were analyzed using the Statistical Package for the Social Sciences.

Results

Thirty six children (22 boys and 16 girls) and their families were included. The mean (SD) age of the children was 11.5?±?6.87 y, and the mean (SD) duration of dialysis was 28?±?11.32 mo. Only one third of the families had the opportunity to choose the modality of dialysis. Both modalities of dialysis had a negative effect on fathers’ jobs in over 50 % of the cases. Similarly, both modalities of treatment had a considerable impact on the quality of care provided by the mothers to other family members. There was no difference between the two modalities on the frequency of admissions.

Conclusions

Both PD and HD had a negative impact on fathers’ jobs and on the level of care provided by mothers to the rest of the family.     

Synthesis and anti‐inflammatory activity of diversified heterocyclic systems

In continuation with our research program on the development of novel bioactive molecules, we report herein the design and synthesis of a series of diversified heterocycles ( 4 – 22 ). The synthesized compounds were evaluated for their anti‐inflammatory activity. The chemical structures of the newly synthesized compounds have been confirmed by NMR, FTIR, and microanalysis.