Edinburgh Napier University

  The majority of clinically used anticancer drugs suffer from poor selectivity for tumour cells over normal healthy cells, leading to poor efficacy and often severe dose-limiting side effects for patients. Chemotherapeutic drugs have a low therapeutic index due to exerting their anticancer effects at or near toxic doses and the development of drug resistance. In this project, new chemical approaches are being developed to improve the therapeutic index and concomitantly reduce significantly the side effects for the patient population.
A series of novel anticancer drugs is being synthesised, characterised and investigated for their selective tumour targeting ability and circumvention of major mechanisms of drug resistance. The novel strategy is exploiting subtle differences between the function of intracellular compartments in cancer cells compared to healthy cells; notably, mitochondria and lysosomes. The clinically used anticancer drug mitoxantrone and structurally related novel aminoanthraquinone derivatives are being linked with specific carriers including triphenylphosphonium bromide (TPP), to transport the drugs through the mitochondrial membrane of cancer cells, visualised by confocal microscopy. Selective accumulation causes tumour cell destruction whilst sparing healthy cells.