Synthesis, antiproliferative and anti-MDR activities of lathyrane diterpene derivatives based on configuration inversion strategy

Xiao, Yao; Ji, Wan-Sheng; Jin, Wenke; Peng, Wen; Shan, Lianhai; Hou, Zong-Rui; Li, Xiaohuan; Zhou, Xian‐Li; Liu, Yanjun; Xu, Jin‐Bu; Gao, Feng

doi:10.1016/j.bioorg.2022.106329

Cited by 4 publications

(1 citation statement)

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“…Several products of natural and/or synthetic origin, such as flavonoids, alkaloids, terpenes and synthetic derivatives of diterpenes, have shown inhibitory potential for transporter function and might reverse MDR phenotype when co-administered with chemotherapeutic drugs. [21][22][23][24][25][26] Some research has suggested that glycolipids are also among the substances that effectively inhibit ABC transport without producing cytotoxic effects. The study of this type of glycoconjugates as a new alternative inhibitor for the ABC transporter is more recent, attributing their efficacy to their complex structures.…”

Section: Introductionmentioning

confidence: 99%

Glycolipids from Sargassum filipendula, a Natural Alternative for Overcoming ABC Transporter‐Mediated MDR in Cancer

Muñoz‐Losada,

Da Costa,

Muñoz‐Castiblanco

et al. 2023

Chemistry & Biodiversity

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Chemotherapy is a widely used strategy to treat cancer, a disease that causes millions of deaths each year. However, its efficacy is reduced by the overexpression of ABC transporters, which are proteins that expel the drugs used in chemotherapy and involved in the multidrug resistance (MDR). Glycolipids have been identified as potential inhibitors of ABC transporters. Algae of the genus Sargassum contain high levels of glycolipids, being a promising therapeutic alternative against the MDR phenotype. Sargassum filipendula glycolipids were obtained by exhaustive maceration with chloroform/methanol, purified by column and thin layer chromatography, and then characterized by FTIR, NMR, and LC‐MS. Cell viability by PI labeling and inhibition of ABC transporters were analyzed by flow cytometry. Assessment of resistance reversal was determined by MTT assay. Ten sulfoquinovosylglycerol‐type compounds were found, and six of them are reported for the first time. Moiety 4 (GL‐4) showed strong and moderate inhibitory activity against ABCC1 and ABCB1 transporters, respectively. Treatment of GL‐4 in combination with the antineoplastic drug vincristine sensitized Lucena‐1 cell model to drug and reversed the MDR phenotype. This is the first report of glycolipids isolated from S. filipendula capable of inhibiting ABC transporters and thus overcoming acquired drug resistance.

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