p-[bis(chloro-2-ethyl)amino]-L-phenylalanine (melphalan) is an approved anti-cancer agent with a broad spectrum of antitumor activity. However, it has some disadvantages, such as poor water-solubility followed by rapid elimination, which reduce the target specificity. To solve these problems, porphyrin- poly(amidoamine) or PAMAM-conjugates of melphalan were synthesized and characterized. The dendrimeric conjugates showed satisfactory water solubility. It was found that the size of the dendrimer played a crucial role in controlling the drug content and diameter of the melphalan-conjugates. The in vitro studies of cell cytotoxicity revealed that by employing the dendrimeric conjugation strategy and using the PAMAM dendritic arms as spacers, the conjugates had good anti-cancer activity and lower toxicity than free melphalan.
Keywords: PAMAM; Porphyrin; anti-cancer activity; dendrimers; melphalan.