2. Academic Validation
  3. Thieno[2,3-b]pyridines--a new class of multidrug resistance (MDR) modulators

Thieno[2,3-b]pyridines--a new class of multidrug resistance (MDR) modulators

  • Bioorg Med Chem. 2014 Nov 1;22(21):5860-70. doi: 10.1016/j.bmc.2014.09.023.
Aivars Krauze 1,  Signe Grinberga 2,  Laura Krasnova 2,  Ilze Adlere 2,  Elina Sokolova 2,  Ilona Domracheva 2,  Irina Shestakova 2,  Zigmars Andzans 2,  Gunars Duburs 2
Affiliations

Affiliations

  • 1 Latvian Institute of Organic Synthesis, 21 Aizkraukles St., Riga LV-1006, Latvia. Electronic address: krauze@osi.lv.
  • 2 Latvian Institute of Organic Synthesis, 21 Aizkraukles St., Riga LV-1006, Latvia.
PMID: 25311564 DOI: 10.1016/j.bmc.2014.09.023
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.

Keywords

Breast cancer resistance protein; Multidrug resistance modulators; Multidrug resistance-associated protein; P-glycoprotein; Thieno[2,3-b]pyridine.

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