Mechanistic Studies on Aziridinyl-Benzoquinones in Cultured Tumour Cells
| المصدر: | مجلة القلعة |
|---|---|
| الناشر: | جامعة المرقب - كلية الآداب والعلوم بمسلاته |
| المؤلف الرئيسي: | Ben Rabha, Fatma M. (Author) |
| مؤلفين آخرين: | Elashheb, Mabruka S. (Co-Author) , Saeed, Nagat M. (Co-Author) , Hassan, Samia Abd Alkarim Ali (Co-Author) , Ben Saad, Lamees A. (Co-Author) |
| المجلد/العدد: | ع7 |
| محكمة: | نعم |
| الدولة: |
ليبيا |
| التاريخ الميلادي: |
2017
|
| الشهر: | يونيو |
| الصفحات: | 690 - 712 |
| رقم MD: | 891630 |
| نوع المحتوى: | بحوث ومقالات |
| اللغة: | الإنجليزية |
| قواعد المعلومات: | HumanIndex |
| مواضيع: | |
| رابط المحتوى: |
عدد مرات التحميل
2
| المستخلص: |
This study compares the anti tumour effects of the novel NQO1 activated drug RH1 (2, 5-diaziridinyl-3 -hydoxymethyl-6-methyl-1, 4- benzoquinone) with a novel lipophilic ester derivative Es5 on the isogenic cell lines MDA 468 and MDA 468 NQO1 which differs only in expression of wtNQO1. A 39- fold enhancement of growth inhibitory activity was seen in NQO1 expressing cells compared the NQO1 null cells for the Es5 compared to the 25- fold increase seen for the parent drug, RH1. The kinetics of cell cycle arrest, apoptosis are different in the NQO1 expressing and null cell lines. This indicates a different mechanism of activations and/ or activity for these agents in the presence of active NQO1 protein. We show that Es5 has a higher partition coefficient than RH1, which may enable Es5 to enter the brain. Following cleavage of the ester group Es5 produces a Quinone whose cytoxicity profile is comparable to RH1. |
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