Lamellarin O, a Pyrrole Alkaloid from an Australian Marine Sponge, Ianthella sp., Reverses BCRP Mediated Drug Resistance in Cancer Cells

Huang, Xiaocong; Xiao, Xue; Zhang, Yun-Kai; Talele, Tanaji T.; Salim, Angela A.; Chen, Zhe‐Sheng; Capon, Robert J.

doi:10.3390/md12073818

Cited by 63 publications

(48 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was found that compound 115 exhibited an increase in intracellular concentration of MX (3.05-fold, 94.5%, 20 μM), which was comparable to that of FTC (82, 3.17-fold, 100%, 10 μM), indicating 115 as a promising ABCG2 modulator. 104…”

Section: Miscellaneous Natural Products and Their Derivativesmentioning

confidence: 99%

ABCG2/BCRP: Specific and Nonspecific Modulators

Peña-Solórzano

Stark

König

et al. 2016

Medicinal Research Reviews

View full text Add to dashboard Cite

Multidrug resistance (MDR) in cancer cells is the development of resistance to a variety of structurally and functionally nonrelated anticancer drugs. This phenomenon has become a major obstacle to cancer chemotherapy seriously affecting the clinical outcome. MDR is associated with increased drug efflux from cells mediated by an energy-dependent mechanism involving the ATP-binding cassette (ABC) transporters, mainly P-glycoprotein (ABCB1), the MDR-associated protein-1 (ABCC1), and the breast cancer resistance protein (ABCG2). The first two transporters have been widely studied already and reviews summarized the results. The ABCG2 protein has been a subject of intense study since its discovery as its overexpression has been detected in resistant cell lines in numerous types of human cancers. To date, a long list of modulators of ABCG2 exists and continues to increase. However, little is known about the clinical consequences of ABCG2 modulation. This makes the design of novel, potent, and nontoxic inhibitors of this efflux protein a major challenge to reverse MDR and thereby increase the success of chemotherapy. The aim of the present review is to describe and highlight specific and nonspecific modulators of ABCG2 reported to date based on the selectivity of the compounds, as many of them are effective against one or more ABC transport proteins.

show abstract

Section: Miscellaneous Natural Products and Their Derivativesmentioning

confidence: 99%

ABCG2/BCRP: Specific and Nonspecific Modulators

Peña-Solórzano

Stark

König

et al. 2016

Medicinal Research Reviews

View full text Add to dashboard Cite

show abstract

“…Compound 38 was 16 folds more sensitive than verapamil in doxorubicin-resistant Lo Vo/Dx cell line, and it increased the cytotoxicity of doxorubin, vinblastine, and daunorubicine in MDR cells because it directly inhibited P-gp pump function and increased drug accumulation in the cells [102]. Lamellarin O (41) is relevant as a multiple P-gp, BCRP, and MRP1 inhibitor [96], but synthetic analogs of 41, designed by QSAR studies and incorporating the methoxyacetophenone moiety unit, did not show BCRP inhibitory activity [103]. This study also allowed to establish some SAR features: bromo or mono-/dimethyl substituents on the indole moiety (Aryl-R 2 ) in lamellarin O (41) lead to a decrease in the BCRP inhibitory activity [103] ( Figure 8).…”

Section: Lamellarins and Derivativesmentioning

confidence: 99%

“…Lamellarin O (41) is relevant as a multiple P-gp, BCRP, and MRP1 inhibitor [96], but synthetic analogs of 41, designed by QSAR studies and incorporating the methoxyacetophenone moiety unit, did not show BCRP inhibitory activity [103]. This study also allowed to establish some SAR features: bromo or mono-/dimethyl substituents on the indole moiety (Aryl-R 2 ) in lamellarin O (41) lead to a decrease in the BCRP inhibitory activity [103] ( Figure 8). were isolated from many marine organisms such as a prosobranch mollusk (Lamellaria sp.)…”

Section: Lamellarins and Derivativesmentioning

confidence: 99%

Marine Natural Products as Models to Circumvent Multidrug Resistance

et al. 2016

View full text Add to dashboard Cite

Multidrug resistance (MDR) to anticancer drugs is a serious health problem that in many cases leads to cancer treatment failure. The ATP binding cassette (ABC) transporter P-glycoprotein (P-gp), which leads to premature efflux of drugs from cancer cells, is often responsible for MDR. On the other hand, a strategy to search for modulators from natural products to overcome MDR had been in place during the last decades. However, Nature limits the amount of some natural products, which has led to the development of synthetic strategies to increase their availability. This review summarizes the research findings on marine natural products and derivatives, mainly alkaloids, polyoxygenated sterols, polyketides, terpenoids, diketopiperazines, and peptides, with P-gp inhibitory activity highlighting the established structure-activity relationships. The synthetic pathways for the total synthesis of the most promising members and analogs are also presented. It is expected that the data gathered during the last decades concerning their synthesis and MDR-inhibiting activities will help medicinal chemists develop potential drug candidates using marine natural products as models which can deliver new ABC transporter inhibitor scaffolds.

show abstract

“…In this context, the pyridine ring is the second most recurrent ring (after phenyl) in the small‐molecule drug list of the FDA Orange Book, but is also present in manifold agrochemicals . The pyrrole ring can be found in numerous natural products (e. g., lamellarin O, I ) as well as in the aforementioned list, albeit it is relatively less frequent in drugs (Figure ). Nevertheless, the best‐selling pharmaceutical within the recent past, atorvastatin ( II , a cholesterol‐lowering agent), is comprised of a polysubstituted pyrrole ring .…”

Section: Introductionmentioning

confidence: 99%

Substrate‐Controlled Divergent Synthesis of Enaminones and Pyrroles from Indolizines and Nitroso Compounds

González-Soria

Alonso

2019

Adv Synth Catal

View full text Add to dashboard Cite

It is imperative to learn new synthetic transformations to succeed in drug discovery and development. We report the substrate-driven synthesis of β-enaminones and N-aryl pyrroles from indolizines and nitrosoarenes; aryl-substituted indolizines lead to β-enaminones in a regio-and diastereoselective manner, whereas alkyl-substituted indolizines produce tetrasubstituted pyrroles. All products contain a pyridine unit, the second most abundant ring (after phenyl) in the FDA Orange Book. In both cases, the reactions proceed at room temperature without any catalyst. Moreover, both types of products can be obtained in one pot from commercial materials as well as at a gram scale. It is worthy of note that the regioselectivity of the βenaminones is inaccessible by the standard literature methods and their utility has been exemplified in the synthesis of diverse heterocycles. We have made every endeavor to put forward the corresponding reaction mechanisms based on thorough experimental work.

show abstract

Lamellarin O, a Pyrrole Alkaloid from an Australian Marine Sponge, Ianthella sp., Reverses BCRP Mediated Drug Resistance in Cancer Cells

Cited by 63 publications

References 27 publications

ABCG2/BCRP: Specific and Nonspecific Modulators

ABCG2/BCRP: Specific and Nonspecific Modulators

Marine Natural Products as Models to Circumvent Multidrug Resistance

Substrate‐Controlled Divergent Synthesis of Enaminones and Pyrroles from Indolizines and Nitroso Compounds

Contact Info

Product

Resources

About