Ningalins, Pyrrole‐Bearing Metabolites Isolated from Didemnum spp. Synthesis and MDR‐Reversion Activity in Cancer Therapy

Abstract

Multi‐Drug Resistance (MDR) is one of the most frequent problems observed in the course of cancer chemotherapy. Cells under treatment, tend to develop survival mechanisms to drug‐action thus generating drug‐resistance. One of the most important mechanism to get it is the over expression of P‐gp glycoprotein, which acts as an efflux‐pump releasing the drug outside of the cancer cell. A strategy for a succesfull treatment consists in the co‐administration of one compound that acts against P‐gp and another which acts against the cell during chemotherapy. Ningalins are pyrrole‐containing naturally occurring compounds isolated mainly from the marine tunicate Didemnum spp and also they are some of the top reversing agents in MDR treatment acting on P‐gp. Considering the relevance displayed for some of these isolated alkaloids or their core as a drug for co‐administration in cancer therapy, all the total synthesis described to date for the members of ningalins family are reviewed herein.