Discovery of traditional Chinese medicine monomers and their synthetic intermediates, analogs or derivatives for battling P-gp-mediated multi-drug resistance

Ma, Xiaodong; Hu, Mengqi; Wang, Hao; Li, Jiaming

doi:10.1016/j.ejmech.2018.09.061

Cited by 38 publications

(25 citation statements)

References 117 publications

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“…An increasing number of pure compounds derived from Chinese medicine herbs have been shown to inhibit the development of cancers through various mechanisms [27][28][29][30]. Besides, a large number of studies have revealed that Chinese medicines in combination with conventional chemotherapy and radiotherapy could increase the therapeutic efficacy and decrease the serious side effects and complications of these therapies [31,32]. It is convinced that Chinese medicines are gaining increasing reputation and credibility as adjuvant therapies for cancer prevention and treatment.…”

Section: Chinese Medicines and Cancer Treatmentmentioning

confidence: 99%

Chinese Medicines for Cancer Treatment from the Metabolomics Perspective

Guo¹,

Tan²,

Wang³

et al. 2020

Metabolomics - New Insights Into Biology and Medicine

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Cancer is one of the most prevalent diseases all over the world with poor prognosis and the development of novel therapeutic strategies is still urgently needed. The large amount of successful experiences in fighting against cancer-like diseases with Chinese medicine has suggested it as a great source of alternative treatments to human cancers. Cancer cells have been shown to own a predominantly unique metabolic phenotype to facilitate their rapid proliferation. Metabolic reprogramming is a remarkable hallmark of cancer and therapies targeting cancer metabolism can be highly specific and effective. Based on the sophisticated study of small molecule metabolites, metabolomics can provide us valuable information on dynamically metabolic responses of living systems to certain environmental condition. In this chapter, we systematically reviewed recent studies on metabolism-targeting anticancer therapies based on metabolomics in terms of glucose, lipid, amino acid, and nucleotide metabolisms and other altered metabolisms, with special emphasis on the potential of metabolic treatment with pure compounds, herb extracts, and formulations from Chinese medicines. The trends of future development of metabolism-targeting anticancer therapies were also discussed. Overall, the elucidation of the underlying molecular mechanism of metabolism-targeting pharmacologic therapies will provide us a new insight to develop novel therapeutics for cancer treatment.

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Section: Chinese Medicines and Cancer Treatmentmentioning

confidence: 99%

Chinese Medicines for Cancer Treatment from the Metabolomics Perspective

Guo¹,

Tan²,

Wang³

et al. 2020

Metabolomics - New Insights Into Biology and Medicine

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“…Many cancers develop drug resistance over time, and one main mechanism for this is drug efflux generated by the overexpression of membrane protein pumps that results in ineffective drugs or low drug concentrations . P‐glycoprotein (P‐gp)‐mediated multidrug resistance (MDR) is a predominant phenotype that hampers patients' responses to chemotherapy . Numerous studies have demonstrated that cancer therapies induce autophagy, which supports cancer cell survival and contributes to therapy resistance .…”

Section: Artemisinin‐induced Autophagy‐dependent Mechanism In Cancer mentioning

confidence: 99%

“…155 P-glycoprotein (P-gp)mediated multidrug resistance (MDR) is a predominant phenotype that hampers patients' responses to chemotherapy. 156 Numerous studies have demonstrated that cancer therapies induce autophagy, which supports cancer cell survival and contributes to therapy resistance. 157,158 The inhibition of autophagy can thus sensitize resistant cancer cells to anticancer drugs and overcome multidrug resistance.…”

mentioning

confidence: 99%

“…157,158 The inhibition of autophagy can thus sensitize resistant cancer cells to anticancer drugs and overcome multidrug resistance. 157,[159][160][161] More recently, 156 researchers have reported that certain traditional Chinese medicines such as artemisinin and its derivatives can combate multidrug resistance. Drug resistance-related genes, such as MDR1, P-gp, multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP), have been shown to have little impact on the efficacy of artemisinin compounds.…”

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confidence: 99%

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Targeting autophagy enhances the anticancer effect of artemisinin and its derivatives

Sun

Yan

Zou

et al. 2019

Medicinal Research Reviews

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Artemisinin and its derivatives, with their outstanding clinical efficacy and safety, represent the most effective and impactful antimalarial drugs. Apart from its antimalarial effect, artemisinin has also been shown to exhibit selective anticancer properties against multiple cancer types both in vitro and in vivo. Specifically, our previous studies highlighted the therapeutic effects of artemisinin on autophagy regulation. Autophagy is a well‐conserved degradative process that recycles cytoplasmic contents and organelles in lysosomes to maintain cellular homeostasis. The deregulation of autophagy is often observed in cancer cells, where it contributes to tumor adaptation to nutrient‐deficient tumor microenvironments. This review discusses recent advances in the anticancer properties of artemisinin and its derivatives via their regulation of autophagy, mitophagy, and ferritinophagy. In particular, we will discuss the mechanisms of artemisinin activation in cancer and novel findings regarding the role of artemisinin in regulating autophagy, which involves changes in multiple signaling pathways. More importantly, with increasing failure rates and the high cost of the development of novel anticancer drugs, the strategy of repurposing traditional therapeutic Chinese medicinal agents such as artemisinin to treat cancer provides a more attractive alternative. We believe that the topics covered here will be important in demonstrating the potential of artemisinin and its derivatives as safe and potent anticancer agents.

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“…[12,13] Although within analogous sets of compounds (e. g. propafenone, tetrahydroisoquinoline, tariquidar and chalcone derivatives, alkaloids, and flavonoids), a clear structure-activity relationship (SAR) pattern was observed, a general and conclusive model is still missing. [14][15][16][17][18][19] Numerous SAR studies suggested that there is a strong correlation between lipophilicity and P-gp inhibitory potency and that active compounds commonly possess at least one aromatic ring, a basic nitrogen atom, and several hydrophobic regions. [12] Preference of P-gp toward lipophilic compounds can be explained by the widely accepted model of substrate transport, which proposes that P-gp extracts its ligands directly from the inner leaflet of the plasma membrane.…”

mentioning

confidence: 99%

Propafenone analogue with additional H‐bond acceptor group shows increased inhibitory activity on P‐glycoprotein

Cseke

Schwarz

Jain

et al. 2020

Archiv der Pharmazie

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P‐glycoprotein (P‐gp) is an ATP‐dependent efflux pump that has a marked impact on the absorption, distribution, and excretion of therapeutic drugs. As P‐gp inhibition can result in drug–drug interactions and altered drug bioavailability, identifying molecular properties that are linked to inhibition is of great interest in drug development. In this study, we combined chemical synthesis, in vitro testing, quantitative structure–activity relationship analysis, and docking studies to investigate the role of hydrogen bond (H‐bond) donor/acceptor properties in transporter–ligand interaction. In a previous work, it has been shown that propafenone analogs with a 4‐hydroxy‐4‐piperidine moiety exhibit a generally 10‐fold higher P‐gp inhibitory activity than expected based on their lipophilicity. Here, we specifically expanded the data set by introducing substituents at position 4 of the 4‐phenylpiperidine moiety to assess the importance of H‐bond donor/acceptor features in this region. The results suggest that indeed an H‐bond acceptor, such as hydroxy and methoxy, increases the affinity by forming a H‐bond with Tyr310.

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Discovery of traditional Chinese medicine monomers and their synthetic intermediates, analogs or derivatives for battling P-gp-mediated multi-drug resistance

Cited by 38 publications

References 117 publications

Chinese Medicines for Cancer Treatment from the Metabolomics Perspective

Chinese Medicines for Cancer Treatment from the Metabolomics Perspective

Targeting autophagy enhances the anticancer effect of artemisinin and its derivatives

Propafenone analogue with additional H‐bond acceptor group shows increased inhibitory activity on P‐glycoprotein

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