期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 59, 期 14, 页码 6729-6738出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.6b00252
关键词
-
资金
- University of Turin, Grant Ricerca Locale-GUGSRILO13
P-glycoprotein (P-gp) is a well-known membrane transporter expressed in a number of strategic biological barriers, where it exerts a protective effect of paramount importance. Conversely it is one of the main causes of multidrug resistance (MDR), being capable of effluxing many chemotherapeutics. In a development of previous research, a small library of compounds was created conjugating diversely substituted furazan rings with MC70, a well-known P-gp inhibitor. These compounds were assessed for their potency against P-gp and another transporter (MRP1), for their apparent permeability (P-app) and for their ability to induce ATPase activity, thus delineating a complete functional profile. They displayed a substrate mechanism of action and high selectivity toward P-gp, unlike the lead compound. Data relating to their activity range from low micromolar to sub-nanomolar EC50, the most interesting compounds being 15 (0.97 nM), 19 (1.3 nM), 25 (0.60 nM), and 27 (0.90 nM).
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