Novel Anti-malarial Atovaquone P rodrug: Synthesis,Characterization and in vitro Kinetics Study

الموضوعات

طب

الملخص

Malaria is a global public health problem, resulting in tow million deaths per year .Themajority of death cases are due to the most severe form of malaria caused by Plasmodiumfalciparum. As a result, efforts were directed toward the development of new effectivemedications intended for the treatment of this endemic disease. Atovaqoune is a newtreatment option, showed an improvement in malaria treatment. Although Atovaqoune isan effective medication, it has its own limitations.Atovaqoune is highly lipophilic compound (water solubility < 0.2 µg/ mL), has low watersolubility and low absorption, hence low bioavailability (< 10% in the fasted state).Accordingly, increasing atovaqoune aqueous solubility will improve its pharmacokineticprofile in particular bioavailability, thus improving its effectiveness and ability toadminister the drug through different routs of administration.So that, our goal was to develop atovaqoune prod rug that possesses increased aqueoussolubility by linking water soluble moiety to the 3- hydroxyl group, via chemical synthesis.Purification techniques including extraction, re-crystallization and column chromatographywere used. Identity confirmation was done using, IR, NMR and LC/MS. Based on purityand identity results; in vitro kinetic studies using the HPLC instrument were performed atpH 2.2, 5.5 and 7.4.ATQ succinate (ProD1) has been successfully synthesized, purified and evaluated. T1/2 ofProD1 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 plottedgives a straight line, and the Kobs is nearly constant. Concisely, modifying atovaqounestructure may result in enhancing its pharmacokinetic profile mainly absorption into bodytissues, consequently increasing efficacy and ability to formulate atovaqoune in differentdosage forms.Keywords: Malaria, drug resistance, atovaquone, bioavailability, prodrugs .

روابط وملفات

التعريف والنوع

رقم الوثيقة

f64c1f88-24a6-4f28-b368-82cae838d9d0

رقم العقد

0

نوع الوسائط

Crawler

نوع المحتوى

الرسائل العلمية

صيغة المصدر

رسائل ماجيستير

نوع الملف

pdf text

أسماء الملفات

1696923_1.pdf

بيانات النشر

ترجمة العنوان

تطوير دواء اولي مبتكر للاتوفاكوون? الدواء المضاد للملاريا: تصنيع كيميائي, تشخيص و تقييم القوى المحركه المخبريه

ألقاب المؤلفين

[{"name_ar":"بيسان وضاح امين الفتاش","title_ar":"اعداد","title_en":"Preparation"},{"name_ar":"رفيق قرمان","title_ar":"اشراف","title_en":"Supervision"}]

اللغة

English

المصدر والدورية

اسم المصدر

Novel Anti-malarial Atovaquone P rodrug: Synthesis,Characterization and in vitro Kinetics Study

المحتوى والصفحات

عدد الصفحات

0

إشراف وإعداد

الإشراف

رفيق قرمان

الإعداد

بيسان وضاح امين الفتاش

الاقتباسات الببليوغرافية