Synthesis, Characterization and In Vitro Kinetics of Amoxicillin and Cephalexin Antibacterial Prodrugs

الموضوعات

طب

الملخص

Marketed antibacterial drugs suffer several problems, such as bitter taste and low stabilitywhich lead to patient incompliance. Prodrug technology for solving such problems isextremely exciting. Based on previously reported density functional theory calculations,amoxicillin ProD 1-2 and cephalexin ProD 1-2 were designed and synthesized. For theintraconversion of both antibacterial prodrugs the kobs and t1/2 values in different mediawere calculated from the linear regression equation obtained from the correlation of logconcentration of the residual prodrug versus time. At constant temperature and pH thehydrolysis reaction for the above mentioned prodrugs displayed strict first order kinetics asthe kobs was quite constant and a straight line was obtained. Kinetic studies in 1N HCl, pH2.5 and pH 5 were selected to examine the intraconversion of both prodrugs to their parentdrugs. The acid-catalyzed hydrolysis of the prodrugs was found to be much higher in 1NHCl than in pH 2.5 and pH 5. The experimental t1/2 values of amoxicillin ProD 1 in 1NHCl, pH 2.5 and pH 5 were 2.5, 7 and 81 hours respectively and for cephalexin ProD 1 in1 N HCl and pH 2.5 were 2 and 14 hours respectively. In contrast, t1/2 values of amoxicillinProD 2 in 1N HCl and pH 2.5 were 8 and 44 hours respectively and for cephalexin ProD 2in 1 N HCl was 6 hours. On the other hand, at pH 7.4, the four prodrugs were quite stableand no release of the parent drugs was observed. At pH 5 the hydrolysis of the prodrugswas too slow. The four antibacterial prodrugs were found to be bitterless. The bitter tastemasking by the prodrugs is believed to be via altering the ability of the drug to interactwith bitter taste receptors.

روابط وملفات

التعريف والنوع

رقم الوثيقة

f526269d-638b-4438-8333-ba6b027bad4e

رقم العقد

0

نوع الوسائط

Crawler

نوع المحتوى

الرسائل العلمية

صيغة المصدر

رسائل ماجيستير

نوع الملف

pdf text

أسماء الملفات

1696926_1.pdf

بيانات النشر

ترجمة العنوان

التركيب الكيميائي والخصائص والقوى المحركة المخبرية لدوائيْن أوليّيْن جديديْن مبتكريْن من مضادات البكتيريا؛ الأموكسيلين والسيفالكسين

ألقاب المؤلفين

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اللغة

English

المصدر والدورية

اسم المصدر

Synthesis, Characterization and In Vitro Kinetics of Amoxicillin and Cephalexin Antibacterial Prodrugs

المحتوى والصفحات

عدد الصفحات

0

إشراف وإعداد

الإشراف

رفيق قرمان

الإعداد

غدير عبد مطر دقماق

الاقتباسات الببليوغرافية