ملخص
The drug efflux pump P-glycoprotein (P-gp) has been shown to promote multidrug resistance (MDR) in tumors as well as to influence ADME properties of drug candidates. Here we synthesized and tested a series of benzophenone derivatives structurally analogous to propafenone-type inhibitors of P-gp. Some of the compounds showed ligand efficiency and lipophilic efficiency (LipE) values in the range of compounds which entered clinical trials as MDR modulators. Interestingly, although lipophilicity plays a dominant role for P-gp inhibitors, all compounds investigated showed LipE values below the threshold for promising drug candidates. Docking studies of selected analogues into a homology model of P-glycoprotein suggest that benzophenones show an interaction pattern similar to that previously identified for propafenone-type inhibitors.
اللغة الأصلية | English |
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الصفحات (من إلى) | 3261-3273 |
عدد الصفحات | 13 |
دورية | Journal of Medicinal Chemistry |
مستوى الصوت | 55 |
رقم الإصدار | 7 |
المعرِّفات الرقمية للأشياء | |
حالة النشر | Published - أبريل 12 2012 |
منشور خارجيًا | نعم |
ASJC Scopus subject areas
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