دراسة حوسبية متكاملة لمشتقات بنزويل ثينوبيريميدين كمنظمات محتملة لمستقبل الإستروجين Erα في علاج سرطان الثدي
DOI:
https://doi.org/10.35516/jjps.v18i2.2805الكلمات المفتاحية:
سرطان الثدي، النمذجة الحوسبية، الامتصاص والتوزيع والتمثيل والإخراج، السمّية، الثينوبيريميدين، العلاقة الكمية ثلاثية الأبعاد بين البنية والنشاطالملخص
يُعدّ سرطان الثدي المعتمد على الهرمونات والموجب لمستقبلات الإستروجين (ER+) هو النوع الأكثر شيوعًا لدى النساء حيث يمثل حوالي 75٪ من جميع الحالات. تهدف هذه الدراسة إلى اقتراح عوامل علاجية جديدة محتملة لسرطان الثدي باستخدام الطرق الحوسبية تم إجراء دراسة ثلاثية الأبعاد للعلاقة الكمية بين البنية والنشاط (3D-QSAR) على 22) مركبًا مستندة إلى أبحاث سابقة، وقد أظهرت قدرة تنبؤية قوية كما يتضح من القيم العالية لـ Q²، والتي بلغت 0.516 و0.787 لطريقتي CoMFA وCoMSIA على التوالي. تم اقتراح ست جزيئات جديدة (T1–T6) بهدف تعزيز النشاط المثبط، وقد أظهرت نتائج تحليل الارتباط الجزيئي أن الجزيئات المرشحة أحرزت نتائج مميزة واستقرت في موقع الارتباط داخل المستقبل رمز PDB: 1SJ0) ) كما أظهرت المركبات المقترحة خصائص دوائية وحركية حيوية مناسبة، باستثناء T3 الذي أظهر سمية خفيفة. وأكدت محاكاة الديناميكيات الجزيئية أن المعقدين T1–1SJ0 و2D–1SJ0 مستقران في الموقع الفعّال لمستقبل الإستروجين Erα تسلط هذه النتائج الضوء على إمكانيات المركبات المبنية على الثينوبيريميدين كمضادات محتملة لسرطان الثدي، مما يفتح آفاقًا جديدة للبحث التجريبي والسريري.
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