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Molecules 2016, 21(7), 892; doi:10.3390/molecules21070892

Marine Natural Products as Models to Circumvent Multidrug Resistance

1
Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Porto 4050-313, Portugal
2
Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), Porto 4050-123, Portugal
3
Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto 4050-123, Portugal
*
Author to whom correspondence should be addressed.
Academic Editor: Helena Vasconcelos
Received: 14 June 2016 / Revised: 27 June 2016 / Accepted: 1 July 2016 / Published: 8 July 2016
(This article belongs to the Special Issue New Approaches to Counteract Drug Resistance in Cancer)

Abstract

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. View Full-Text
Keywords: ABC transporters; P-glycoprotein modulators; marine natural products; multidrug resistance (MDR); synthesis; structure activity relationship (SAR) ABC transporters; P-glycoprotein modulators; marine natural products; multidrug resistance (MDR); synthesis; structure activity relationship (SAR)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Long, S.; Sousa, E.; Kijjoa, A.; Pinto, M.M.M. Marine Natural Products as Models to Circumvent Multidrug Resistance. Molecules 2016, 21, 892.

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