Water-soluble porphyrin-PAMAM-conjugates of melphalan and their anticancer activity

Abstract

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:

• Porphyrin
• PAMAM
• dendrimers
• melphalan
• anti-cancer activity

Acknowledgements

We would like to thank Rios O. H., Velasco L., Huerta S. E., Patiño M. M. R., Peña Gonzalez M. A., Rios Ruiz L. F. García-Hernández, F. Jaimes-Miranda and García Rios E. for technical assistance.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by CONACyT [220675] and DGAPA [IN101117] grants. EMK was supported by a postdoctoral fellowship from DGAPA-UNAM.