Jatrophane diterpenes and cancer multidrug resistance – ABCB1 efflux modulation and selective cell death induction

Reis, Mariana; Ahmed, Omar Bauomy; Spengler, Gabriella; Molnár, Joséph; Lage, Hermann; Ferreira, Maria‐José U.

doi:10.1016/j.phymed.2016.05.007

Cited by 44 publications

(38 citation statements)

References 35 publications

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“…In addition, the formation of a rare C5-O-C13 bridge would increase the activity, while epoxidation of D 12 is detrimental to the activity (Zhu et al 2016). Reis et al (2016) screened jatrophanes euphowelwitschine A (1), euphowelwitschine B (2), welwitschene (267), epoxywelwitschene (268) and esulatin M (134) for MDR resistance activity through a combination of Rho123 efflux and chemoreversal assays on adriamycin resistant human hepatocellular carcinoma cell line HepG2 (HepG2/ADR) and adriamycin resistant human mammary adenocarcinoma cell line MCF-7 (MCF-7/ADR). 1, 267, 268, and 134 showed to be able to revert the MDR phenotype, at 20 lM, being two-fold (1 and 134) and three-fold (267 and 268) more effective than 'verapamil' (FAR = 12.5 at 20 lM) (Reis et al 2016).…”

Section: Mdr Reversing Activitymentioning

confidence: 99%

“…Reis et al (2016) screened jatrophanes euphowelwitschine A (1), euphowelwitschine B (2), welwitschene (267), epoxywelwitschene (268) and esulatin M (134) for MDR resistance activity through a combination of Rho123 efflux and chemoreversal assays on adriamycin resistant human hepatocellular carcinoma cell line HepG2 (HepG2/ADR) and adriamycin resistant human mammary adenocarcinoma cell line MCF-7 (MCF-7/ADR). 1, 267, 268, and 134 showed to be able to revert the MDR phenotype, at 20 lM, being two-fold (1 and 134) and three-fold (267 and 268) more effective than 'verapamil' (FAR = 12.5 at 20 lM) (Reis et al 2016). In assays on EPG85-257RNOV cells which have been done previously, 268 caused a 4.5-fold increase of total apoptosis and 134 showed a 2.6-fold increase.…”

Section: Mdr Reversing Activitymentioning

confidence: 99%

“…The compounds 268 and 134 appear particularly interesting, due to their dual activity: as ABCB1 modulators and MDR-selective anti-proliferative compounds. SAR results that high conformational flexibility of the twelve-membered ring of jatrophanes 267, 268, and 134 favored ABCB1 modulation, in contrast to the 5/8/8 fused ring system of euphowelwitschines A (1) and B (2) (Reis et al 2016). Mai et al (2017a, b) isolated heliosterpenoids A and B (50 and 51) with a novel 5/6/4/6-fused tetracyclic ring skeleton, from E. helioscopia.…”

Section: Mdr Reversing Activitymentioning

confidence: 99%

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Jatrophane and rearranged jatrophane-type diterpenes: biogenesis, structure, isolation, biological activity and SARs (1984–2019)

et al. 2020

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Diterpene compounds specially macrocyclic ones comprising jatrophane, lathyrane, terracinolide, ingenane, pepluane, paraliane, and segetane skeletons occurring in plants of the Euphorbiaceae family are of considerable interest in the context of natural product drug discovery programs. They possess diverse complex skeletons and a broad spectrum of therapeutically relevant biological activities including anti-inflammatory, anti-chikungunya virus, anti-HIV, cytotoxic, and multidrug resistance-reversing activities as well as curative effects on thrombotic diseases. Among macrocyclic diterpenes of Euphorbia, the discovery of jatrophane and modified jatrophane diterpenes with a wide range of structurally unique polyoxygenated polycyclic derivatives and as a new class of powerful inhibitors of P-glycoprotein has opened new frontiers for research studies on this genus. In this review, an attempt has been made to give in-depth coverage of the articles on the naturally occurring jatrophanes and rearranged jatrophane-type diterpenes isolated from species belonging to the Euphorbiaceae family published from 1984 to March 2019, with emphasis on the biogenesis, isolation methods, structure, biological activity, and structureactivity relationship.

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Section: Mdr Reversing Activitymentioning

confidence: 99%

Section: Mdr Reversing Activitymentioning

confidence: 99%

Section: Mdr Reversing Activitymentioning

confidence: 99%

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Jatrophane and rearranged jatrophane-type diterpenes: biogenesis, structure, isolation, biological activity and SARs (1984–2019)

et al. 2020

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“…Drug metabolism processes like absorption, transportation, metabolism, and clearance are very important for the treatment efficacy of the diseases [71]. For example, overexpression of the P-glycoprotein (P-gp) result in drug resistance [72] and it has been reported that inhibition of it can improve the drug efficacy [73][74][75] and participate in drug synergistic effect. Drug metabolism processes should be considered in future combinatorial drug prediction models.…”

Section: Discussionmentioning

confidence: 99%

In-Silico Methodologies for Cancer Multidrug Optimization

Hasan¹,

Eldin

Khedr

et al. 2018

IJCT

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Drug combinations is considered as an effective strategy designed to control complex diseases like cancer. Combinations of drugs can effectively decrease side effects and enhance adaptive resistance. Therefore, increasing the likelihood of defeating complex diseases in a synergistic way. This is due to overcoming factors such as off-target activities, network robustness, bypass mechanisms, cross-talk across compensatory escape pathways and the mutational heterogeneity which results in alterations within multiple molecular pathways. The plurality of effective drug combinations used in clinic were found out through experience. The molecular mechanisms underlying these drug combinations are often not clear. It is not easy to suggest new drug combinations. Computational approaches are proposed to reduce the search space for defining the most promising combinations and prioritizing their experimental evaluation. In this paper, we review methods, techniques and hypotheses developed for in silico methodologies for drug combination discovery in cancer and discuss the limitations and challenges of these methods.

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“…Drug metabolism processes such as drug absorption and transportation are very important in disease treatment [81]. For example, one of the most important reasons for drug resistance is the overexpression of the P-glycoprotein (P-gp) [82], a drug efflux protein expressed by ABCB1 which is from ATP-binding cassette (ABC) family [83–85], and it has been reported that inhibition of P-gp can enhance the drug efficacy [86–90]. Thus, we deduced that drugs inhibiting efflux genes (e.g., ABC family genes) or activating drug influx genes (e.g., solute carrier transporter genes [91]) can make a contribution to drug synergistic effect.…”

Section: Discussionmentioning

confidence: 99%

Biomolecular Network-Based Synergistic Drug Combination Discovery

Qin

Yang

et al. 2016

BioMed Research International

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Drug combination is a powerful and promising approach for complex disease therapy such as cancer and cardiovascular disease. However, the number of synergistic drug combinations approved by the Food and Drug Administration is very small. To bridge the gap between urgent need and low yield, researchers have constructed various models to identify synergistic drug combinations. Among these models, biomolecular network-based model is outstanding because of its ability to reflect and illustrate the relationships among drugs, disease-related genes, therapeutic targets, and disease-specific signaling pathways as a system. In this review, we analyzed and classified models for synergistic drug combination prediction in recent decade according to their respective algorithms. Besides, we collected useful resources including databases and analysis tools for synergistic drug combination prediction. It should provide a quick resource for computational biologists who work with network medicine or synergistic drug combination designing.

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Jatrophane diterpenes and cancer multidrug resistance – ABCB1 efflux modulation and selective cell death induction

Cited by 44 publications

References 35 publications

Jatrophane and rearranged jatrophane-type diterpenes: biogenesis, structure, isolation, biological activity and SARs (1984–2019)

Jatrophane and rearranged jatrophane-type diterpenes: biogenesis, structure, isolation, biological activity and SARs (1984–2019)

In-Silico Methodologies for Cancer Multidrug Optimization

Biomolecular Network-Based Synergistic Drug Combination Discovery

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