Abstract：
:Treatment of cancer patients with chemotherapeutic drugs is often associated with the occurrence of tumors with a multidrug resistance (MDR). Furthermore, the relation between overexpression of P-glycoprotein (P-gp) and resistant cancers has been well established. In this study, novel 2-aminobenzofuran derivatives were synthesized and tested for their ability to modulate P-gp mediated multidrug resistance (MDR) in vitro. The most potent compound, 43, increased P-gp inhibitory activity at 5 μM by 11.12-fold and was 3.6-fold stronger than verapamil. Furthermore, 43 can sensitize Flp-In™-293/MDR cells toward vincristine, paclitaxel and doxorubicin by 17.95-fold, 13.68-fold and 26.43-fold at 2.5 μM, respectively. 43 also can sensitize the resistant cancer cell line KBvin toward vincristine, paclitaxel and doxorubicin by 246.43-fold, 38.72-fold and 5.16-fold at 2.5 μM, respectively. In conclusion, important aspects for developing potent P-gp inhibitors have been emphasized in this study, providing a starting point for the further structural optimization of P-gp inhibitors.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Chen CY,Lin CM,Lin HC,Huang CF,Lee CY,Si Tou TC,Hung CC,Chang CSdoi
10.1016/j.ejmech.2016.08.044subject
Has Abstractpub_date
2017-01-05 00:00:00pages
1023-1035eissn
0223-5234issn
1768-3254pii
S0223-5234(16)30697-3journal_volume
125pub_type
杂志文章abstract：:The aldehyde oxidases (AOXs) are a small sub-family of cytosolic molybdo-flavoenzymes, which are structurally conserved proteins and broadly distributed from plants to animals. AOXs play multiple roles in both physiological and pathological processes and AOX inhibition is of increasing significance in the development ...
journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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doi：10.1016/j.ejmech.2011.02.008
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journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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