Antineoplastic produgs activated by cellular hypoxia

Abstract

[EN]The general objective of this Thesis is the design and synthesis of moieties that can be attached to antineoplastic drugs, to produce anticancer prodrugs able of selectively attacking cancer cells without affecting healthy ones. The generated prodrugs activation is due to cancer microenvironment features exploitation, in which the drug carriers are functionalised with a disulfide bond or a nitro group, the latter can be reduced under the intrinsic factors such as hypoxia and the high concertation of glutathione for an in-situ release of the cytotoxic drug. As a result, side effects of conventional chemotherapy could be avoided. In addition to the above, the afforded prodrugs could be theranostic agents thanks to the fluorescent effect of the cyclized trigger obtained following the prodrug cleavage under the mentioned conditions. The molecular trigger was also employed as a new protecting group for amines and amino acids. These prodrugs were functionalized to be soluble in aqueous media to avoid the problems of many anticancer drugs which are known to be hydrophobic.