Epoxylathyrol Derivatives: Modulation of ABCB1-Mediated Multidrug Resistance in Human Colon Adenocarcinoma and Mouse T-Lymphoma Cells

Journal of Natural Products
Ana M MatosMaria-José U Ferreira

Abstract

Epoxyboetirane A (1), a macrocyclic diterpene that was found to be inactive as an ABCB1 modulator, was submitted to several chemical transformations, aimed at generating a series of compounds with improved multidrug resistance (MDR)-modifying activity. Overall, 23 new derivatives were prepared, in addition to the already reported epoxylathyrol (2) and methoxyboetirol (3). Their anti-MDR potential was assessed through both functional and chemosensitivity assays on resistant human colon adenocarcinoma and human ABCB1-gene transfected L5178Y mouse lymphoma cells. Structure-activity relationship analysis showed that different substitution patterns led to distinct ABCB1 inhibitory activities, although intrinsic cellular characteristics seemed to influence the modulatory behavior. A considerable enhancement in MDR-modifying activity was observed for aromatic compounds in both cell lines, particularly in 3,17-disubstituted esters derived from 3, a Payne-rearranged Michael adduct of 2. All compounds tested were revealed to interact synergistically with doxorubicin, and ATPase inhibition by three representative MDR-modifying compounds was also investigated. On account of its outstanding ABCB1 inhibitory activity at 0.2 μM and overall re...Continue Reading

References

Jun 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·I PastanM C Willingham
May 28, 1993·International Journal of Cancer. Journal International Du Cancer·J L WeaverA Aszalos
Oct 25, 2003·Oncogene·Suresh V AmbudkarMichael M Gottesman
Sep 18, 2007·Eukaryotic Cell·Kailash Gulshan, W Scott Moye-Rowley
Jan 8, 2008·Planta medica·Noélia DuarteMaria-José U Ferreira
Jun 27, 2008·Cellular and Molecular Life Sciences : CMLS·H Lage
Dec 2, 2009·Methods in Molecular Biology·Chow H Lee
May 25, 2011·Journal of Chemical Information and Modeling·Ricardo J FerreiraRita C Guedes
Jun 19, 2012·Annual Review of Microbiology·Rajendra Prasad, Andre Goffeau
Jan 23, 2013·Journal of Medicinal Chemistry·Mariana ReisMaria-José U Ferreira
Dec 3, 2014·Bioorganic & Medicinal Chemistry·Cátia VieiraMaria-José U Ferreira
Jan 3, 2015·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Rishil J KathawalaZhe-Sheng Chen

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Citations

Apr 23, 2016·Future Medicinal Chemistry·Rafael BaptistaMaria-José U Ferreira
Jul 9, 2016·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Mariana Alves ReisMaria-José U Ferreira
Apr 20, 2017·Journal of Natural Products·Mariana A ReisMaria-José U Ferreira
Mar 24, 2018·Future Medicinal Chemistry·Ricardo J FerreiraMaria-José U Ferreira
Jul 29, 2016·Natural Product Reports·James R Hanson
Aug 22, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Csaba BúsAndrea Vasas
Jul 30, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Bruno M F GonçalvesMaria-José U Ferreira
Apr 4, 2017·Phytotherapy Research : PTR·Muhammad Torequl Islam
May 28, 2020·Frontiers in Pharmacology·Mariana Alves ReisMaria-José U Ferreira
Apr 8, 2020·Phytotherapy Research : PTR·Ting XuYumeng Wei
Sep 4, 2016·Bioorganic & Medicinal Chemistry·Cátia RamalheteMaria-José U Ferreira
Dec 14, 2017·Bioorganic & Medicinal Chemistry·Angela PaternaMaria-José U Ferreira
Feb 13, 2017·European Journal of Medicinal Chemistry·Angela PaternaMaria-José U Ferreira

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