title: Potent galloyl-based selective modulators targeting multidrug resistance associated protein 1 and P-glycoprotein.
abstract: The multifactorial nature of chemotherapy failure in controlling cancer is often associated with the occurrence of multidrug resistance (MDR), a phenomenon likely related to the increased expression of members of the ATP binding cassette (ABC) transporter superfamily. In this respect, the most extensively characterized MDR transporters include ABCB1 (also known as MDR1 or P-glycoprotein) and ABCC1 (also known as MRP1) whose inhibition remains a priority to circumvent drug resistance. Herein, we report how the simple galloyl benzamide scaffold can be easily and properly decorated for the preparation of either MRP1 or P-gp highly selective inhibitors. In particular, some gallamides and pyrogallol-1-monomethyl ethers showed remarkable affinity and selectivity toward MRP1. On the other hand, trimethyl ether galloyl anilides, with few exceptions, exhibited moderate to very high and selective P-gp inhibition.
authors: Dipartimento Farmaco-Chimico, Università degli Studi di Bari "Aldo Moro", Via Orabona 4, 70125 Bari, Italy.
authors: Raffaella Zoe
authors: RZ
authors: Pellicani
authors: Angela
authors: A
authors: Stefanachi
authors: Mauro
authors: M
authors: Niso
authors: Angelo
authors: A
authors: Carotti
authors: Francesco
authors: F
authors: Leonetti
authors: Orazio
authors: O
authors: Nicolotti
authors: Roberto
authors: R
authors: Perrone
authors: Francesco
authors: F
authors: Berardi
authors: Saverio
authors: S
authors: Cellamare
authors: Nicola Antonio
authors: NA
authors: Colabufo
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000813:Anilides / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001549:Benzamides / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D004285:Dogs; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004355:Drug Stability; D004987:Ethers / Q000138:chemical synthesis / Q000494:pharmacology; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D011748:Pyrogallol / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000813:Anilides; D000970:Antineoplastic Agents; D001549:Benzamides; D004987:Ethers; D011748:Pyrogallol; D005707:Gallic Acid