title: Thieno[2,3-b]pyridines--a new class of multidrug resistance (MDR) modulators.
abstract: To identify new potent multidrug resistance modulators, we have synthesized a series of novel thieno[2,3-b]pyridines and furo[2,3-b]pyridines, and examined their structure-activity relationships. All synthesized compounds were tested to determine BCRP1, P-gp, and MRP1 inhibitor activity, and most potent MDR modulators were also screened for their toxicity, cytotoxicity and Ca(2+) channel antagonist activity. Among these compounds, thieno[2,3-b]pyridine (6r) was found to exhibit a potent P-gp inhibitory action with EC50 = 0.3 ± 0.2 μM, MRP1 inhibitory action with EC50 = 1.1 ± 0.1 μM and BCRP1 inhibitory action with EC50 = 0.2 ± 0.05 μM and may represent suitable candidate for further pharmacological studies.
authors.affiliation: Latvian Institute of Organic Synthesis, 21 Aizkraukles St., Riga LV-1006, Latvia. Electronic address: krauze@osi.lv.
authors.forename: Aivars
authors.initials: A
authors.lastname: Krauze
authors.affiliation: Latvian Institute of Organic Synthesis, 21 Aizkraukles St., Riga LV-1006, Latvia.
authors.forename: Signe
authors.initials: S
authors.lastname: Grinberga
authors.affiliation: Latvian Institute of Organic Synthesis, 21 Aizkraukles St., Riga LV-1006, Latvia.
authors.forename: Laura
authors.initials: L
authors.lastname: Krasnova
authors.affiliation: Latvian Institute of Organic Synthesis, 21 Aizkraukles St., Riga LV-1006, Latvia.
authors.forename: Ilze
authors.initials: I
authors.lastname: Adlere
authors.affiliation: Latvian Institute of Organic Synthesis, 21 Aizkraukles St., Riga LV-1006, Latvia.
authors.forename: Elina
authors.initials: E
authors.lastname: Sokolova
authors.affiliation: Latvian Institute of Organic Synthesis, 21 Aizkraukles St., Riga LV-1006, Latvia.
authors.forename: Ilona
authors.initials: I
authors.lastname: Domracheva
authors.affiliation: Latvian Institute of Organic Synthesis, 21 Aizkraukles St., Riga LV-1006, Latvia.
authors.forename: Irina
authors.initials: I
authors.lastname: Shestakova
authors.affiliation: Latvian Institute of Organic Synthesis, 21 Aizkraukles St., Riga LV-1006, Latvia.
authors.forename: Zigmars
authors.initials: Z
authors.lastname: Andzans
authors.affiliation: Latvian Institute of Organic Synthesis, 21 Aizkraukles St., Riga LV-1006, Latvia.
authors.forename: Gunars
authors.initials: G
authors.lastname: Duburs
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D006801:Humans; D051379:Mice; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009130:Muscle, Smooth / Q000378:metabolism; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D013329:Structure-Activity Relationship; D058924:Thienopyridines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D002118:Calcium; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D058924:Thienopyridines; C116614:ABCG2 protein, human; C421109:multidrug resistance-associated protein 1
keywords: Breast cancer resistance protein; Multidrug resistance modulators; Multidrug resistance-associated protein; P-glycoprotein; Thieno[2,3-b]pyridine