Flavonoid derivatives as selective ABCC1 modulators: Synthesis and functional characterization

European Journal of Medicinal Chemistry
José Esteban Obreque-BalboaArmin Buschauer

Abstract

A series of chromones, bearing substituted amino groups or N-substituted carboxamide moieties in position 2, was synthesized and characterized in cellular assays for modulation of the ABC transporters ABCC1 (MDCKII-MRP1 cells), ABCB1 (Kb-V1 cells) and ABCG2 (MCF-7/Topo cells). The most potent ABCC1 modulators identified among these flavonoid-type compounds were comparable to the reference compound reversan regarding potency, but superior in terms of selectivity concerning ABCB1 and ABCG2 (2-[4-(Benzo[c][1,2,5]oxadiazol-5-ylmethyl)piperazin-1-yl]-5,7-dimethoxy-4H-chromen-4-one (51): ABCC1, IC50 11.3 μM; inactive at ABCB1 and ABCG2). Compound 51 was as effective as reversan in reverting ABCC1-mediated resistance to cytostatics in MDCKII-MRP1 cells and proved to be stable in mouse plasma and cell culture medium. Modulators, such as compound 51, are of potential value as pharmacological tools for the investigation of the (patho)physiological role of ABCC1.

References

Jan 1, 1992·Journal of Cancer Research and Clinical Oncology·G BernhardtH Schönenberger
Mar 1, 1988·The Journal of Cell Biology·P BoukampN E Fusenig
Dec 1, 1985·Environmental Health Perspectives·S N Moreno, R Docampo
Nov 21, 1998·The Journal of Biological Chemistry·E BakosB Sarkadi
Mar 31, 1999·Bioorganic & Medicinal Chemistry Letters·M RoeP Charlton
Mar 21, 2002·Nature Reviews. Cancer·Michael M GottesmanSusan E Bates
Jan 18, 2003·Journal of Pharmaceutical Sciences·Hang NguyenMarilyn E Morris
May 16, 2003·Journal of Medicinal Chemistry·Mohamed HadjeriJean Boutonnat
Nov 18, 2003·Cellular and Molecular Life Sciences : CMLS·D TrompierA Di Pietro
Apr 23, 2005·Toxicology and Applied Pharmacology·Elaine M LeslieSusan P C Cole
Jun 2, 2005·Bioorganic & Medicinal Chemistry·Ahmed S Mehanna, Jin Yung Kim
Sep 3, 2005·European Journal of Medicinal Chemistry·Ziad OmranSylvain Rault
Apr 1, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Michelle HaberMurray D Norris
Jun 20, 2006·Bioorganic & Medicinal Chemistry·Maria KoufakiAlexandros Makriyannis
Aug 29, 2006·Nature Chemical Biology·Karson S PuttPaul J Hergenrother
Oct 9, 2007·Trends in Microbiology·Amy L Davidson, Peter C Maloney
Oct 13, 2007·Journal of Cancer Research and Clinical Oncology·Martina HubensackArmin Buschauer
May 1, 2009·Human Genomics·Vasilis VasiliouDaniel W Nebert
Oct 2, 2009·Journal of Medicinal Chemistry·Michel PerezBruno Le Grand
Mar 1, 2011·Bioorganic & Medicinal Chemistry Letters·Dhanaji Achyutrao ThoratAe Nim Pae
May 17, 2011·Bioorganic & Medicinal Chemistry Letters·Cristian Ochoa PuentesBurkhard König
Dec 15, 2011·Journal of Medicinal Chemistry·Glaucio ValdameriAttilio Di Pietro
Mar 1, 2012·Journal of the American Society for Mass Spectrometry·Yunfeng ChaiYuanjiang Pan
Sep 18, 2012·Bioorganic & Medicinal Chemistry Letters·Girish D HatnapureVandana M Kamble
Sep 21, 2013·Annual Review of Pharmacology and Toxicology·Susan P C Cole
Apr 11, 2013·ACS Medicinal Chemistry Letters·Cristian Ochoa-PuentesBurkhard König
Jan 3, 2015·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Rishil J KathawalaZhe-Sheng Chen
Jun 11, 2015·Future Medicinal Chemistry·Ricardo J FerreiraMaria-José U Ferreira

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Citations

May 18, 2016·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Jamie I FletcherMichelle Haber
Dec 23, 2016·Medicinal Research Reviews·Diana Peña-SolórzanoCristian Ochoa-Puentes
Mar 24, 2018·Future Medicinal Chemistry·Ricardo J FerreiraMaria-José U Ferreira
Jul 31, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ni ZhangWei-Dong Pan
Aug 25, 2020·Pharmaceutical Chemistry Journal·Noor Ul Amin MohsinUsman Saleem
Jul 30, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Bruno M F GonçalvesMaria-José U Ferreira
Apr 18, 2019·Beilstein Journal of Organic Chemistry·Peng LiHaihong Huang
Sep 10, 2020·Frontiers in Pharmacology·Xiaofang LuoZhe-Sheng Chen
Aug 3, 2019·Bioorganic Chemistry·Niccolò ChiaramonteMaria Novella Romanelli
Feb 12, 2021·Journal of Medicinal Chemistry·Ross S ManciniMark A Reed
Feb 6, 2020·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Jinyun DongJiang-Jiang Qin
Feb 28, 2020·European Journal of Medicinal Chemistry·Frauke AntoniGünther Bernhardt
Mar 17, 2021·Journal of Medicinal Chemistry·Vigneshwaran NamasivayamSven Marcel Stefan
May 7, 2021·Frontiers in Pharmacology·Huan XiaoQiu Sun
Jun 19, 2021·Computational and Structural Biotechnology Journal·Vigneshwaran NamasivayamSven Marcel Stefan
Aug 22, 2018·ACS Medicinal Chemistry Letters·Diana Peña-SolórzanoCristian Ochoa-Puentes
May 26, 2017·Journal of Medicinal Chemistry·Joana ReisFernanda Borges
Sep 15, 2021·Chemical Biology & Drug Design·Vaishali M PatilVijay Masand
Dec 11, 2021·Bioinformatics·Vigneshwaran NamasivayamSven Marcel Stefan

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