مثبطات COX-2 جديدة من قاعدة بيانات ZINC ومسح افتراضي لحامل خاصية دوائية 3D لطب الأعشاب وإرساء جزيئي

مثبطات COX-2 جديدة من قاعدة بيانات ZINC ومسح افتراضي لحامل خاصية دوائية 3D لطب الأعشاب وإرساء جزيئي

2021-04-01 | المجلد السادس العدد السادس - المجلد السادس | مقالات بحثية
نتالي موسى | أحمد حسن

الملخص

يعد إنزيم السيكلوأكسيجيناز-2 (COX-2) الهدف الرئيس لمضادات الالتهاب اللا ستيرويدية الانتقائية، وحديثاً هدفاً هاماً للأدوية السرطانية وأدوية الزهايمر. تم في هذه الدراسة، إجراء نمذجة حامل دوائي Pharmacophore modeling، ومسح افتراضي Virtual Screening، وإرساء Docking لتعيين هوية مثبطاتCOX-2  جديدة.

تم بناء نموذجي حاملي دواء A وB لصنفين كيميائيين من مثبطات COX-2. أظهرت نماذج حوامل الخاصية الدوائية الجديدة المظاهر الرئيسة لمثبطات الارتباط بالإنزيم COX-2. واستخدم النموذجان لمسح قاعدة البيانات ALL NOW ZINC وبيانات مكونات عشبية صغيرة بهدف الحصول على مثبطات COX-2 فعالة جديدة.

لتأكيد النتائج حول انتقائية المثبطات، جرى إرساء المكونات المستعادة، الخاضعة لقاعدة Lipiniski`s rule الخامسة (RO5)، في بنية COX-2 3D باستخدام GLIDE. وأخيراً، استناداً على الألفة الرابطة وطرز ارتباط الجزيئات، جرى الحصول على ستة مركبات جديدة كمركبات واعدة يمكن استخدامها كطليعة لاكتشاف مثبطات COX-2 جديدة.


كلمات مفتاحية : Cyclooxygenase-2; Docking; QSAR; Pharmacophore and virtual screening.
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