Pharmaceutical Sciences
Permanent URI for this collection
Browse
Browsing Pharmaceutical Sciences by Author "Dr. Nasr Shraim"
Now showing 1 - 3 of 3
Results Per Page
Sort Options
- Itemتصنيع ودراسة المواصفات والقوى المحركة المخبرية للأدوية المساعدة للدوبامين(AL-Quds University, 2016-12-21) يحيى فؤاد رشيد خواجا; yahya fuad rasheed khawaja; رفيق قرمان; د. حاتم حجازي; Dr. Nasr ShraimParkinson patients have insufficient dopamine in specific regions of the brain, so attempts have been made to replenish the deficiency in the dopamine. Dopamine itself doesn't cross blood brain barrier, but its precursor, levodopa (LD) is actively transported into the CNS and is converted to dopamine in the brain. The bioavailability of LD is less than 10% with only 1% of administered oral levodopa penetrates the brain. Large doses of levodopa are required because much of the drug is decarboxylated to dopamine in the periphery, resulting in side effects that include nausea, vomiting, cardiac arrhythmias, and hypotension. To minimize the conversion to dopamine (DA) outside the central nervous system (CNS), LD is usually co- administered with peripheral inhibitors of amino acid decarboxylase (carbidopa and benserazide). In spite of that, other central nervous side effects such as dyskinesia, on-off phenomenon and end-of-dose deterioration still remain.Based on DFT calculations a novel dopamine prodrugs for the treatment of Parkinson’s disease that can improve the overall biopharmaceutical profile of the current medications to enhance effectiveness and to ease the use of the medications were synthesized, characterized, in vitro intra-conversion to their parent drugs and in silico pharmacokinetics and toxicity prediction were also studied. The synthesized dopamine prodrugs have a carboxylic group as a hydrophilic moiety and a hydrocarbon skeleton as a lipophilic moiety, where the combination of both groups ensures a moderate hydrophilic lipophilc balance value. The potential prodrugs are expected to give better bioavailability than the parental drug owing to improved absorption. Furthermore, these prodrugs are believed to be more effective than L-dopa because the latter undergoes decarboxylation in the periphery before reaching the blood– brain barrier. Additionally, the synthesized prodrugs can be used in different dosage forms (I.V., S.C., tablets, and others) because of their potential solubility in organic and aqueous media. For dopamine ProD 1 the experimental t½ values in 0.1N HCl, buffer pH 2.2, buffer pH 5.5 and buffer pH 7.4 were 60.3 hours, 54.66 hours, 99.93 hours and 138.13 hours, respectively. Dopamine ProD 2 was readily converted in 0.1N HCl, buffer pH 2.2, pH 5.5 and pH 7.4 with half -life time (t½) of 48.34 hours, 54.22 hours, 131.98 hours and 193.42 hours, respectively. Finally, in silico predicting of physiochemical parameters, ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) properties, oral bioavailability and BBB permeability for the synthesized prodrugs were studied. The results revealed that no prodrug had a high risk of toxicity, and all the prodrugs showed good pharmacokinetic properties. Moreover, all synthesized dopamine prodrugs were found to obey Lipinski’s rule of five.
- Itemتطوير دواء اولي مبتكر للاتوفاكوون? الدواء المضاد للملاريا: تصنيع كيميائي, تشخيص و تقييم القوى المحركه المخبريه(AL-Quds University, 2016-01-05) بيسان وضاح امين الفتاش; Beesan Waddah Amin Alfattash; رفيق قرمان; د أحمد عمرو; Dr. Nasr ShraimMalaria is a global public health problem, resulting in tow million deaths per year .The majority of death cases are due to the most severe form of malaria caused by Plasmodium falciparum. As a result, efforts were directed toward the development of new effective medications intended for the treatment of this endemic disease. Atovaqoune is a new treatment option, showed an improvement in malaria treatment. Although Atovaqoune is an effective medication, it has its own limitations. Atovaqoune is highly lipophilic compound (water solubility < 0.2 µg/ mL), has low water solubility and low absorption, hence low bioavailability (< 10% in the fasted state). Accordingly, increasing atovaqoune aqueous solubility will improve its pharmacokinetic profile in particular bioavailability, thus improving its effectiveness and ability to administer the drug through different routs of administration. So that, our goal was to develop atovaqoune prod rug that possesses increased aqueous solubility by linking water soluble moiety to the 3- hydroxyl group, via chemical synthesis. Purification techniques including extraction, re-crystallization and column chromatography were used. Identity confirmation was done using, IR, NMR and LC/MS. Based on purity and identity results; in vitro kinetic studies using the HPLC instrument were performed at pH 2.2, 5.5 and 7.4. ATQ succinate (ProD1) has been successfully synthesized, purified and evaluated. T1/2 of ProD1 at pH 2.2, 5.5 and 7.4 is 28.8 days, 2.2 days, 3.2 days, respectively. It can be concluded from these data, that ProD1 is converted into ATQ in pH dependentmanner, and the hydrolysis of the prodrug follows first order kinetics, as the data plotted gives a straight line, and the Kobs is nearly constant. Concisely, modifying atovaqoune structure may result in enhancing its pharmacokinetic profile mainly absorption into body tissues, consequently increasing efficacy and ability to formulate atovaqoune in different dosage forms. Keywords: Malaria, drug resistance, atovaquone, bioavailability, prodrugs .
- Itemدراسة العلاقة الكمية بين الفاعلية والصيغة البنائية باستخدام طريقتي (MLR وPC-ANN ) لبعض المركبات التي لها فعالية على بروتين Translocator (TSPO(AL-Quds University, 2016-01-05) هناء سليم حسين بني عودة; hanaa Saleem Hussein Baniowda; عمر ذيب; رفيق قرمان; Dr. Nasr ShraimQuantitative structure-activity relationship study was performed to understand the activity of a set of 136 ligands of Translocator protein (TSPO) compounds. QSAR models were developed using multiple linear regression (MLR) as linear method. While principal component - artificial neural networks (PC-ANN) modeling method was used as nonlinear method. The results obtained offer good regression models having good prediction ability. The MLR resulted with models (12-24) which have coefficient of determination (R 2 ) >0.6, the best model (number 24) resulted with correlation coefficient (R) = 0.909, coefficient of determination (R 2 ) = 0.826, and adjusted coefficient of determination (R 2 adj) = 0.788. Cross Validation leave one out (LOO) and leave many out (LMO) were performed on the resulted MLR models, models 19-24 showed a good predictive power. After that principle component analysis (PCA) performed to divide the data into three data sets, then the ANN performed on the chosen models (19-24) from leave one out (LOO) and leave many out (LMO) validation. ANN resulted models were validated through randomization test, then the conditions proposed by Golbraikh and Tropsha were applied to conclude that the QSAR models has acceptable prediction power or not. However the best ANN model with a good predictivepower was model #24, with R test values 0.832