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Keywords = lamellarin O

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20 pages, 1262 KB  
Article
Lamellarin O, a Pyrrole Alkaloid from an Australian Marine Sponge, Ianthella sp., Reverses BCRP Mediated Drug Resistance in Cancer Cells
by Xiao-Cong Huang, Xue Xiao, Yun-Kai Zhang, Tanaji T. Talele, Angela A. Salim, Zhe-Sheng Chen and Robert J. Capon
Mar. Drugs 2014, 12(7), 3818-3837; https://doi.org/10.3390/md12073818 - 27 Jun 2014
Cited by 75 | Viewed by 9239
Abstract
ATP binding cassette (ABC) transporters, such as P-gp, BCRP and MRP1, can increase efflux of clinical chemotherapeutic agents and lead to multi-drug resistance (MDR) in cancer cells. While the discovery and development of clinically useful inhibitors has proved elusive to date, this molecular [...] Read more.
ATP binding cassette (ABC) transporters, such as P-gp, BCRP and MRP1, can increase efflux of clinical chemotherapeutic agents and lead to multi-drug resistance (MDR) in cancer cells. While the discovery and development of clinically useful inhibitors has proved elusive to date, this molecular target nevertheless remains a promising strategy for addressing and potentially overcoming MDR. In a search for new classes of inhibitor, we used fluorescent accumulation and efflux assays supported by cell flow cytometry and MDR reversal assays, against a panel of sensitive and MDR human cancer cell lines, to evaluate the marine sponge co-metabolites 112 as inhibitors of P-gp, BCRP or MRP1 initiated MDR. These studies identified and characterized lamellarin O (11) as a selective inhibitor of BCRP mediated drug efflux. A structure–activity relationship analysis inclusive of the natural products 112 and the synthetic analogues 1319, supported by in silico docking studies, revealed key structural requirements for the lamellarin O (11) BCRP inhibitory pharmacophore. Full article
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