Discovery of alkoxyl biphenyl derivatives bearing dibenzo[c,e]azepine scaffold as potential dual inhibitors of P-glycoprotein and breast cancer resistance protein

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.

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“…Together with the previous findings, the results suggest that the compound may be a dual modulator of ABCB1 and ABCG2. 182…”

Section: Heavy Metalsmentioning

confidence: 99%

ABCG2/BCRP: Specific and Nonspecific Modulators

Peña-Solórzano

Stark

König

et al. 2016

Medicinal Research Reviews

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“…Aryloxazole and arylthiazole derivative series have been developed for improving the P-gp selectivity. 70 The P-gp activity of these derivatives was decreased and showed increased BCRP and MRP1 inhibition activity. Different substituent on the aryl chain has been substituted for modulating the activity towards the MDR transporters (BCRP/P-gp/MRP1).…”

Section: Naphthalenyl Derivativesmentioning

confidence: 98%

A review on BCRP inhibitors: An upcoming strategy for cancer treatment

Kaur¹,

Bhandari²

2020

ATMPH

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Worldwide. Cancer is the most terrified disease and major cause of death. Every year approximately, 1.6 million new cases of cancer are being diagnosed worldwide and extensive research efforts are in going on for finding a cure to this life-threatening disease. Till date several thousand synthetic compounds and numerous natural products have been evaluated biologically as anticancer agents. The main disappointment of cancer treatment is multidrug resistance (MDR) which is linked with the over expression of certain protein transporters of ATP binding cassette (ABC). Among 48 ABC transporters, p-glycoprotein (p-gp), multidrug resistance protein 1(MDRP1), breast cancer resistance proteins (BCRP) are efflux transporters which are mainly associated with MDR. ABCG2/ BCRP is supposed to have importance in protection from regulating oral bioavailability, xenobiotics, and also known to have role in forming part of blood-testis barrier, blood-brain barrier and maternal-fetal barrier. BCRPs also expressed in stem cells, where it acts a role in protecting from xenobiotics. Due to broad substrate selectivity of BCRP, it might also impact the pharmacokinectics of many other unrelated drug including anti-HIV drugs, anticancer and endogenous compounds Breast cancer resistance protein (BCRP/ABCG2) is an ABC-transporter which is present in luminal layer of epithelial cells of intestine that limits absorption of many of drugs such as methotrexate, topotecan, mitoxantrone and doxorubicin (anticancers).In this review we want to present the role of BCRP in failure of chemotherapy and its inhibitors for the reversal of MDR. The main theme of the article will be BCRP inhibitors: An upcoming strategy for cancer treatment.

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“…Dibenz[c,e]azepine derivatives attract the attention of synthetic and medicinal chemists due to their potential use in human and veterinary medicine. This scaffold is present in the vasodilator azapetine [1], as well as in a broad variety of compounds exhibiting anticancer [2][3][4][5][6][7][8], anti-inflammatory [9], hypolipidemic [10,11], and other types of biological activities [6,[12][13][14][15][16][17][18]. In addition, dibenz[c,e]azepines have been used as chiral organocatalysts in enantioselective synthesis [19,20].…”

Section: Introductionmentioning

confidence: 99%

4b,5,6,9-Tetrahydro-7H-dibenzo[c,e]pyrrolo[1,2-a]azepin-7-one

Boichenko

Babkin

Kobylskoy

et al. 2019

Molbank

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A simple approach to synthesize 4b,5,6,9-tetrahydro-7H-dibenzo[c,e]pyrrolo[1,2-a]azepin- 7-one has been developed, based on a three-step transformation of 2-(2-bromophenyl)cyclopropane-1,1-diester. The key stage in this method is an intramolecular cross-coupling of 1-(2-bromobenzyl)-5-(2-bromophenyl)pyrrolidin-2-one under continuous flow conditions in an H-Сube-Pro using commercially available supported Pd catalysts.

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Discovery of alkoxyl biphenyl derivatives bearing dibenzo[c,e]azepine scaffold as potential dual inhibitors of P-glycoprotein and breast cancer resistance protein

Cited by 13 publications

References 9 publications

ABCG2/BCRP: Specific and Nonspecific Modulators

ABCG2/BCRP: Specific and Nonspecific Modulators

A review on BCRP inhibitors: An upcoming strategy for cancer treatment

4b,5,6,9-Tetrahydro-7H-dibenzo[c,e]pyrrolo[1,2-a]azepin-7-one

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