Pharmacy Research
http://hdl.handle.net/10576/3250
2024-03-28T19:30:39Z
-
Structure-activity relationship investigation of methoxy substitution on anticancer pyrimido[4,5-c]quinolin-1(2H)-ones
http://hdl.handle.net/10576/53713
Structure-activity relationship investigation of methoxy substitution on anticancer pyrimido[4,5-c]quinolin-1(2H)-ones
Metwally, Kamel; Khalil, Ashraf; Sallam, Asmaa; Pratsinis, Harris; Kletsas, Dimitris; El Sayed, Khalid
Pyrimido[4,5-c]quinolin-1(2H)-one derivatives were shown to exert interesting biological activities including anticancer, antimicrobial, and cardiovascular. Substitution with methoxy groups played a crucial role in the anticancer activity of known anticancer agents. This study explores the contribution of diverse-positioned methoxy substituents to the antimigratory and cytotoxic activities of this class. Synthesized analogues were tested in the MTT, cell cycle, and wound-healing assays. Previous studies on this class reported weak to medium antimitotic activity. Therefore, all compounds were subjected to tubulin polymerization assay and in silico molecular docking study at the colchicine binding site of tubulin. The 2-methoxy and 2,4-dimethoxy substitutions at the 2-arylpyrimido functionality enhanced the antimigratory activity in the 9-methoxy-substituted series like 6 and 9. The 3,4,5-trimethoxy substitutions at the 2-arylpyrimido group also significantly improved the antimigratory activity in the presence or absence of the 9-methoxy substitution as represented by 13 and 22, respectively. Docking experiments showed two distinct orientations at the colchicine binding site of tubulin. The first, achieved by 7 and 16-20, coincides with that of colchicine and positions the methoxy-substituted 2-aryl ring deep in the highly hydrophobic narrow end of the funnel-shaped binding pocket. On the other hand, 5, 6, 9-14 and 21, were oriented towards the wider opening of the binding pocket. Pyrimido[4,5-c] quinolin-1(2H)-ones are promising antimigratory hits with potential for future use to control metastatic breast cancers. © 2013 Springer Science+Business Media New York.
2013-09-01T00:00:00Z
-
Monoamine oxidase inhibitors extracted from tobacco smoke as neuroprotective factors for potential treatment of Parkinson’s disease
http://hdl.handle.net/10576/53712
Monoamine oxidase inhibitors extracted from tobacco smoke as neuroprotective factors for potential treatment of Parkinson’s disease
Sari, Youssef; Khalil, Ashraf
Parkinson’s disease (PD) is a neurodegenerative disease characterized by the loss of mainly the nigrostriatal dopaminergic neurons, which leads to motor dysfunction. Although, most of the drugs are currently used for symptomatic treatment, there are at least three FDA-approved drugs for the treatment of PD that have been suggested preclinically to have neuroprotective effects. Among these drugs are monoamine oxidase (MAO) type B inhibitors such as selegiline and rasagiline, and non-ergot derivative dopamine agonist, pramipexole. In this review article, we focused on the potential uses of non-selective reversible MAO inhibitor, 2,3,6-trimethyl-1,4-naphthoquinone, from flue-cured tobacco leaves extract and two β- carboline alkaloids (harman and norharman) as potent, reversible and non-selective MAO inhibitors for the treatment of PD. In addition, we discussed the potential uses of farnesol as a potent inhibitor of MAO-B and farnesylacetone as a less potent selective MAO-B inhibitor. Furthermore, adducts of 1,2,3,4-tetrahydroisoquinoline have shown to have competitive inhibitory effects for both MAO-A and MAO-B. These inhibitors have potential neuroprotective effects, which might be mediated at least through nerve growth factor, neurotrophin 3, brain derived neurotrophic factor, and glial-cell-line-derived neurotrophic factor. We suggest here the neuroprotective implication of extracted MAO inhibitors from smoke tobacco; however, it is important to note that there are several existing compounds in tobacco smoke that have toxic effects in the brain, these include and not limited to the induction of neuropathological features observed in individuals suffering from Alzheimer’s disease and dementia.
2015-07-01T00:00:00Z
-
Forging the Path to Precision Medicine in Qatar: A Public Health Perspective on Pharmacogenomics Initiatives
http://hdl.handle.net/10576/53373
Forging the Path to Precision Medicine in Qatar: A Public Health Perspective on Pharmacogenomics Initiatives
Bastaki, Kholoud; Velayutham, Dinesh; Irfan, Areeba; Adnan, Mohd; Mohammed, Sawsan; Mbarek, Hamdi; Qoronfleh, Walid; Jithesh, Puthen Veettil
Pharmacogenomics (PGx) is an important component of precision medicine that promises tailored treatment approaches based on an individual’s genetic information. Exploring the initiatives in research that help to integrate PGx test into clinical setting, identifying the potential barriers and challenges as well as planning the future directions, are all important for fruitful PGx implementation in any population. Qatar serves as an exemplar case study for the Middle East, having a small native population compared to a diverse immigrant population, advanced healthcare system, national genome program, and several educational initiatives on PGx and precision medicine. This paper attempts to outline the current state of PGx research and implementation in Qatar within the global context, emphasizing ongoing initiatives and educational efforts. The inclusion of PGx in university curricula and healthcare provider training, alongside precision medicine conferences, showcase Qatar’s commitment to advancing this field. However, challenges persist, including the requirement for population specific implementation strategies, complex genetic data interpretation, lack of standardization, and limited awareness. The review suggests policy development for future directions in continued research investment, conducting clinical trials for the feasibility of PGx implementation, ethical considerations, technological advancements, and global collaborations to overcome these barriers.
2024-03-18T00:00:00Z
-
Redesigning the clinical pharmacy practice model at a psychiatric hospital
http://hdl.handle.net/10576/53140
Redesigning the clinical pharmacy practice model at a psychiatric hospital
Zolezzi, Monica; Gottstein, Ingo; Nilsson, Benjamin
Introduction: Integrated, patient-centered clinical pharmacy services have been shown to improve patient outcomes in a variety of settings, including mental health. In this article, we describe and report the impact of a restructured clinical practice model that incorporated direct patient care by pharmacists implemented at a psychiatric facility in Edmonton, Canada. The purpose of redesigning the clinical pharmacy program was to deliver proactive pharmacist care through integrated clinical pharmacy services and to better align pharmacists' activities with those that have been reported to have a positive impact on patient outcomes. Methods: Pharmacists' documentation notes in medical records for patients admitted and discharged from the hospital at four different time periods were reviewed. For each time period, the number, type, and documentation rate were measured and compared using a Student t test with correction for unequal variances. Significant change was defined as P,.05. Documentation rates were also compared for short-stay versus long-stay patients. Results: A consistent and statistically significant increase was found in pharmacists' clinical notes per chart from 0.15 to 1.5 (P,.001) after implementation of the redesigned clinical practice model. The proportion of clinical notes also increased from 22% in the preimplementation period to up to 68% in the current period. This indicates that pharmacists were spending proportionally more time on proactive versus reactive care. Documentation rates also increased regardless of the patients' length of stay. Discussion: The redesigned clinical practice model enabled a successful transition of the pharmacists' role, from being predominantly reactive to becoming more proactive and integrated.
2015-01-01T00:00:00Z