Marine Natural Products with P-Glycoprotein  Inhibitor Properties

Lopéz, Dioxelis; Martínez-Luis, Sergio

doi:10.3390/md12010525

Cited by 65 publications

(51 citation statements)

References 103 publications

(155 reference statements)

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“…Lamellarins were isolated from many marine organisms such as a prosobranch mollusk (Lamellaria sp.) [35,95], an ascidian (Daphniphyllum chartaceum), a sponge (Dendrilla cactos), and unidentified ascidians [35]. More than 50 lamellarins have been described and mainly differ in the number and position of hydroxyl and methoxy groups on the common chromenoindoles I scaffold (Figure 8) [96].…”

Section: Lamellarins and Derivativesmentioning

confidence: 99%

“…There are already several reviews which highlighted the importance of marine natural products in cancer and, in particular, as P-gp modulators [29,35,[39][40][41][42][43]. However, this review aims to describe not only the effects of the most valuable scaffolds from marine natural products and analogs in overcoming MDR but also their synthetic pathways.…”

Section: Introductionmentioning

confidence: 99%

“…Marine natural products are one of the most interesting targets for global drug discovery since they not only possess structural and chemical uniqueness but also represent novel scaffolds for drug development [34]. Marine natural products have also been studied and tested alongside with synthetic compounds as ABC transporter inhibitors [29,[35][36][37][38]. The development of anticancer drugs from marine compounds is one of the most promising approaches in drug discovery with therapeutic agents in clinical practice, such as the anticancer trabectedin [37].…”

Section: Introductionmentioning

confidence: 99%

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Marine Natural Products as Models to Circumvent Multidrug Resistance

et al. 2016

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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.

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Section: Lamellarins and Derivativesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Marine Natural Products as Models to Circumvent Multidrug Resistance

et al. 2016

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“…In this review, we discuss marine compounds, their activity as MDR reversal agents, and their impact on the chemotherapy over various malignancies. Recently, Lopez and Martinez-Luis [ 80 ] reported in a review that patellamide d, kendarimide A, bryostatin 1, ISA, ISA B, nocardioazines, discodermolide, and polyoxygenated steroids are also MDR reversal agents (these will not be discussed here).…”

Section: Marine Modulators Of Abc Transportersmentioning

confidence: 99%

ABC Transporter Modulatory Drugs from Marine Sources: A New Approach to Overcome Drug Resistance in Cancer

Patel

Wang

Sim

et al. 2014

Resistance to Targeted Anti-Cancer Therapeutics

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Fighting this unconquerable mammoth of a disease that is cancer has been increasingly diffi cult from its discovery over a century ago. A multitude of agents have been identifi ed in the past to conquer the battle against cancer. Nevertheless, controlling it from its onset has been very diffi cult, the reason being its ability to evade the toxic insults, and to develop mechanisms to survive in the presence of cancer drugs. Of the several factors responsible, the phenomenon of multidrug resistance (MDR) has contributed essentially for the cancerous cells to survive. This phenomenon is characterized by the ability to impart immunity to several classes of drugs with different structural and mechanistic traits. The association of ATP-binding cassette (ABC) effl ux transporters with the development of MDR has been a major impediment toward attaining an effi cient chemotherapeutic outcome in cancer patients. Overcoming this pathway of resistance with the use of modulators to block the drug effl ux transporters has shown some promise in recent years. However, there is still room for improvement in designing the clinical strategy and developing newer agents to overcome MDR. Nature has provided researchers

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“…P-gp inhibitors, as demonstrated by photo-affinity labeling, may exert their inhibitory effect by one of the following three mechanisms: (1) altering P-gp expression; (2) Disrupting the ATP hydrolysis; and (3) competition for a binding site or reversible inhibition. 19 It might be speculated that the P-gp inhibitory mechanisms of cetirizine are both altering P-gp expression and competition for P-gp binding sites. Western blotting results of present study confirm the idea.…”

Section: Discussionmentioning

confidence: 99%