Ningalins, Pyrrole‐Bearing Metabolites Isolated from <i>Didemnum</i> spp. Synthesis and MDR‐Reversion Activity in Cancer Therapy
Luis A. Segura‐Quezada, Edson D. Hernández‐Velázquez, Alma Rosa Corrales Escobosa, Claudia de León‐Solís, César R. Solorio‐Alvarado
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.