title: Synthesis and biological evaluation of (hetero)arylmethyloxy- and arylmethylamine-phenyl derivatives as potent P-glycoprotein modulating agents.
abstract: Starting from lead compounds 12b and 28b, previously characterized as P-glycoprotein (P-gp) modulating agents, two series of new compounds were investigated. Compounds 14a, b and 15a, b displayed high P-gp modulating activity in the submicromolar range (EC 50 values from 0.25 to 0.80 microM). Moreover, amino derivatives 23- 27 showed EC 50 values ranging from 0.085 to 0.90 microM. In the pyridyl series, the best result has been obtained for 4-pyridyl derivative 17b (EC 50 = 0.85 microM). The best P-gp modulating agents 14a, b, 15a, b, and 23- 27 also have been studied for determining their breast cancer resistance protein (BCRP) inhibition activity. The results demonstrated that only the amino derivatives 23- 27 displayed moderate BCRP inhibition activity.
authors.affiliation: Dipartimento farmacochimico, Universita degli Studi di Bari, Bari, Italy. colabufo@farmchim.uniba.it
authors.forename: Nicola Antonio
authors.initials: NA
authors.lastname: Colabufo
authors.forename: Francesco
authors.initials: F
authors.lastname: Berardi
authors.forename: Roberto
authors.initials: R
authors.lastname: Perrone
authors.forename: Simona
authors.initials: S
authors.lastname: Rapposelli
authors.forename: Maria
authors.initials: M
authors.lastname: Digiacomo
authors.forename: Michael
authors.initials: M
authors.lastname: Vanni
authors.forename: Aldo
authors.initials: A
authors.lastname: Balsamo
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors; D001555:Benzene Derivatives / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D001692:Biological Transport; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008744:Methylamines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: C116614:ABCG2 protein, human; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D001555:Benzene Derivatives; D008744:Methylamines; D009363:Neoplasm Proteins; D011725:Pyridines