التوليف والتقييم البيولوجي لمثبطات الأنهايدريز الكربونية III وIV عن طريق كروماتوغرافيا الغاز باستخدام كريات معدلة حساسة لدرجة الحموضة
DOI:
https://doi.org/10.35516/jjps.v16i2.1470الكلمات المفتاحية:
كربونيك أنهايدريز III، كربونيك أنهايدريز IX، مثبطات، أميدات، أحماض هيدروكسيمية، إيمينات، مخلّب الزنكالملخص
تم تصنيع خمسة عشر مركبًا واختبارها كمثبطات محتملة لـلأنهايدريز الكربوني III (CAIII) والأنهايدريز الكربوني IX (CAIX)، ستة منها مركبات جديدة. تم تقييم مشتقات الأميدات (a1-4) والأحماض الهيدروكسيمية (b1-2) والإيمينات (c1-9) لنشاطها المثبط ضد CAIII وCAIX عن طريق كروماتوجرافيا الغاز باستخدام كريات معدلة حساسة لدرجة الحموضة. أظهرت المشتقات نسب تثبيط تتراوح بين 12-56٪ لـ CAIII و44-59٪ لـ CAIX، مقارنة بـ 49٪ و63٪ لكابتوبريل (المركب المرجعي) على التوالي. أظهرت الإيمينات أفضل تثبيط لـ CAIII، بينما أظهرت جميع المشتقات نشاطًا مشابهًا ضد CAIX. من المفترض أن ذرة النيتروجين في شقوق الإيمين أو الأميد أو الحمض الهيدروكسيمي بالقرب من مجموعة قابلة للتأين بالتنسيق مع أيون الزنك في الموقع النشط. علاوة على ذلك، تم اختبار المركبات بالنسبة لنشاطهم المضاد للميكروبات والفطريات. بشكل عام، أظهرت المركبات نشاطًا منخفضًا او عدم النشاط ضد بعض البكتيريا موجبة وسالبة الجرام. هذا يدعم نظرية قدرتها على الارتباط بالأنهايدريز الكربوني البشري ولكن ليس الأنهايدريز الكربوني الخاص بالبكتيريا. يمكن أن تكون هذه المركبات بمثابة نماذج مفيدة لتطوير مثبطات الأنهايدريز الكربونية أكثر فعالية وانتقائية كمضادات للسمنة ومضادة للسرطان.
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